Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Nucleic acid sequences involved in regulating the expression of genes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
Established cell cultures that have the potential to propagate indefinitely.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Cis-acting regulatory sequences in the HIV long terminal repeat (LTR) which play a major role in induction or augmentation of HIV gene expression in response to environmental stimuli such as mitogens, phorbol esters, or other viruses. The HIV enhancer is the binding site for many cellular transcription factors including the nuclear factor NF-kappa B.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
Deoxyribonucleic acid that makes up the genetic material of viruses.
The functional hereditary units of VIRUSES.
Actual loss of portion of a chromosome.
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
Biochemical identification of mutational changes in a nucleotide sequence.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.
A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
The genetic unit consisting of three structural genes, an operator and a regulatory gene. The regulatory gene controls the synthesis of the three structural genes: BETA-GALACTOSIDASE and beta-galactoside permease (involved with the metabolism of lactose), and beta-thiogalactoside acetyltransferase.
Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.
Any method used for determining the location of and relative distances between genes on a chromosome.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A group of chemical elements that are needed in minute quantities for the proper growth, development, and physiology of an organism. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A computer based method of simulating or analyzing the behavior of structures or components.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The functional hereditary units of INSECTS.
Substances that comprise all matter. Each element is made up of atoms that are identical in number of electrons and protons and in nuclear charge, but may differ in mass or number of neutrons.
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
Hormones secreted by insects. They influence their growth and development. Also synthetic substances that act like insect hormones.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A family of low-molecular weight, non-histone proteins found in chromatin.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.
A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.
One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Proteins encoded by adenoviruses that are synthesized prior to, and in the absence of, viral DNA replication. The proteins are involved in both positive and negative regulation of expression in viral and cellular genes, and also affect the stability of viral mRNA. Some are also involved in oncogenic transformation.
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.
Cellular DNA-binding proteins encoded by the c-jun genes (GENES, JUN). They are involved in growth-related transcriptional control. There appear to be three distinct functions: dimerization (with c-fos), DNA-binding, and transcriptional activation. Oncogenic transformation can take place by constitutive expression of c-jun.
Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A SOXE transcription factor that plays a critical role in regulating CHONDROGENESIS; OSTEOGENESIS; and male sex determination. Loss of function of the SOX9 transcription factor due to genetic mutations is a cause of CAMPOMELIC DYSPLASIA.
Genes that encode highly conserved TRANSCRIPTION FACTORS that control positional identity of cells (BODY PATTERNING) and MORPHOGENESIS throughout development. Their sequences contain a 180 nucleotide sequence designated the homeobox, so called because mutations of these genes often results in homeotic transformations, in which one body structure replaces another. The proteins encoded by homeobox genes are called HOMEODOMAIN PROTEINS.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
A genus of potentially oncogenic viruses of the family POLYOMAVIRIDAE. These viruses are normally present in their natural hosts as latent infections. The virus is oncogenic in hosts different from the species of origin.
Nucleic acid regulatory sequences that limit or oppose the action of ENHANCER ELEMENTS and define the boundary between differentially regulated gene loci.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
A cellular transcriptional coactivator that was originally identified by its requirement for the stable assembly IMMEDIATE-EARLY PROTEINS of the HERPES SIMPLEX VIRUS. It is a nuclear protein that is a transcriptional coactivator for a number of transcription factors including VP16 PROTEIN; GA-BINDING PROTEIN; EARLY GROWTH RESPONSE PROTEIN 2; and E2F4 TRANSCRIPTION FACTOR. It also interacts with and stabilizes HERPES SIMPLEX VIRUS PROTEIN VMW65 and helps regulate GENETIC TRANSCRIPTION of IMMEDIATE-EARLY GENES in HERPES SIMPLEX VIRUS.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences.
Activating transcription factors of the MADS family which bind a specific sequence element (MEF2 element) in many muscle-specific genes and are involved in skeletal and cardiac myogenesis, neuronal differentiation and survival/apoptosis.
Transcription factors that were originally identified as site-specific DNA-binding proteins essential for DNA REPLICATION by ADENOVIRUSES. They play important roles in MAMMARY GLAND function and development.
A family of muscle-specific transcription factors which bind to DNA in control regions and thus regulate myogenesis. All members of this family contain a conserved helix-loop-helix motif which is homologous to the myc family proteins. These factors are only found in skeletal muscle. Members include the myoD protein (MYOD PROTEIN); MYOGENIN; myf-5, and myf-6 (also called MRF4 or herculin).
Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
A family of transcription factors that share a unique DNA-binding domain. The name derives from viral oncogene-derived protein oncogene protein v-ets of the AVIAN ERYTHROBLASTOSIS VIRUS.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
Highly repeated sequences, 100-300 bases long, which contain RNA polymerase III promoters. The primate Alu (ALU ELEMENTS) and the rodent B1 SINEs are derived from 7SL RNA, the RNA component of the signal recognition particle. Most other SINEs are derived from tRNAs including the MIRs (mammalian-wide interspersed repeats).
Proteins prepared by recombinant DNA technology.
A ubiquitously expressed octamer transcription factor that regulates GENETIC TRANSCRIPTION of SMALL NUCLEAR RNA; IMMUNOGLOBULIN GENES; and HISTONE H2B genes.
Proteins found in any species of insect.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.
Y-box-binding protein 1 was originally identified as a DNA-binding protein that interacts with Y-box PROMOTER REGIONS of MHC CLASS II GENES. It is a highly conserved transcription factor that regulates expression of a wide variety of GENES.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.
A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.
A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.
Fushi tarazu transcription factors were originally identified in DROSOPHILA. They are found throughout ARTHROPODS and play important roles in segmentation and CENTRAL NERVOUS SYSTEM development.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A plant genus of the family CUCURBITACEAE, order Violales, subclass Dilleniidae best known for cucumber (CUCUMIS SATIVUS) and cantaloupe (CUCUMIS MELO). Watermelon is a different genus, CITRULLUS. Bitter melon may refer to MOMORDICA or this genus.
A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.
A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
An early growth response transcription factor that controls the formation of the MYELIN SHEATH around peripheral AXONS by SCHWANN CELLS. Mutations in EGR2 transcription factor have been associated with HEREDITARY MOTOR AND SENSORY NEUROPATHIES such as CHARCOT-MARIE-TOOTH DISEASE.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Ribonucleic acid that makes up the genetic material of viruses.
Proteins obtained from species of BIRDS.
Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Nucleotide sequences repeated on both the 5' and 3' ends of a sequence under consideration. For example, the hallmarks of a transposon are that it is flanked by inverted repeats on each end and the inverted repeats are flanked by direct repeats. The Delta element of Ty retrotransposons and LTRs (long terminal repeats) are examples of this concept.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Antigens associated with HUMAN T-LYMPHOTROPIC VIRUS 1.
A heterotetrameric transcription factor composed of two distinct proteins. Its name refers to the fact it binds to DNA sequences rich in GUANINE and ADENINE. GA-binding protein integrates a variety of SIGNAL TRANSDUCTION PATHWAYS and regulates expression of GENES involved in CELL CYCLE control, PROTEIN BIOSYNTHESIS, and cellular METABOLISM.
A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.
The posterior of the three primitive cerebral vesicles of an embryonic brain. It consists of myelencephalon, metencephalon, and isthmus rhombencephali from which develop the major BRAIN STEM components, such as MEDULLA OBLONGATA from the myelencephalon, CEREBELLUM and PONS from the metencephalon, with the expanded cavity forming the FOURTH VENTRICLE.
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.
A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns).
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Nucleic acid sequences that are involved in the negative regulation of GENETIC TRANSCRIPTION by chromatin silencing.
The farthest or outermost projections of the body, such as the HAND and FOOT.
Morphological and physiological development of EMBRYOS or FETUSES.
Sequences within RNA that regulate the processing, stability (RNA STABILITY) or translation (TRANSLATION, GENETIC) of RNA.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.
The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.
Species of the genus MASTADENOVIRUS, causing a wide range of diseases in humans. Infections are mostly asymptomatic, but can be associated with diseases of the respiratory, ocular, and gastrointestinal systems. Serotypes (named with Arabic numbers) have been grouped into species designated Human adenovirus A-F.
A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A cell line derived from cultured tumor cells.
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.

Transcriptional repression by the Drosophila giant protein: cis element positioning provides an alternative means of interpreting an effector gradient. (1/7062)

Early developmental patterning of the Drosophila embryo is driven by the activities of a diverse set of maternally and zygotically derived transcription factors, including repressors encoded by gap genes such as Kruppel, knirps, giant and the mesoderm-specific snail. The mechanism of repression by gap transcription factors is not well understood at a molecular level. Initial characterization of these transcription factors suggests that they act as short-range repressors, interfering with the activity of enhancer or promoter elements 50 to 100 bp away. To better understand the molecular mechanism of short-range repression, we have investigated the properties of the Giant gap protein. We tested the ability of endogenous Giant to repress when bound close to the transcriptional initiation site and found that Giant effectively represses a heterologous promoter when binding sites are located at -55 bp with respect to the start of transcription. Consistent with its role as a short-range repressor, as the binding sites are moved to more distal locations, repression is diminished. Rather than exhibiting a sharp 'step-function' drop-off in activity, however, repression is progressively restricted to areas of highest Giant concentration. Less than a two-fold difference in Giant protein concentration is sufficient to determine a change in transcriptional status of a target gene. This effect demonstrates that Giant protein gradients can be differentially interpreted by target promoters, depending on the exact location of the Giant binding sites within the gene. Thus, in addition to binding site affinity and number, cis element positioning within a promoter can affect the response of a gene to a repressor gradient. We also demonstrate that a chimeric Gal4-Giant protein lacking the basic/zipper domain can specifically repress reporter genes, suggesting that the Giant effector domain is an autonomous repression domain.  (+info)

Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers. (2/7062)

Gene expression in higher eukaryotes appears to be regulated by specific combinations of transcription factors binding to regulatory sequences. The Ets factor PU.1 and the IRF protein Pip (IRF-4) represent a pair of interacting transcription factors implicated in regulating B cell-specific gene expression. Pip is recruited to its binding site on DNA by phosphorylated PU.1. PU.1-Pip interaction is shown to be template directed and involves two distinct protein-protein interaction surfaces: (i) the ets and IRF DNA-binding domains; and (ii) the phosphorylated PEST region of PU.1 and a lysine-requiring putative alpha-helix in Pip. Thus, a coordinated set of protein-protein and protein-DNA contacts are essential for PU.1-Pip ternary complex assembly. To analyze the function of these factors in vivo, we engineered chimeric repressors containing the ets and IRF DNA-binding domains connected by a flexible POU domain linker. When stably expressed, the wild-type fused dimer strongly repressed the expression of a rearranged immunoglobulin lambda gene, thereby establishing the functional importance of PU.1-Pip complexes in B cell gene expression. Comparative analysis of the wild-type dimer with a series of mutant dimers distinguished a gene regulated by PU.1 and Pip from one regulated by PU.1 alone. This strategy should prove generally useful in analyzing the function of interacting transcription factors in vivo, and for identifying novel genes regulated by such complexes.  (+info)

A premature termination codon interferes with the nuclear function of an exon splicing enhancer in an open reading frame-dependent manner. (3/7062)

Premature translation termination codon (PTC)-mediated effects on nuclear RNA processing have been shown to be associated with a number of human genetic diseases; however, how these PTCs mediate such effects in the nucleus is unclear. A PTC at nucleotide (nt) 2018 that lies adjacent to the 5' element of a bipartite exon splicing enhancer within the NS2-specific exon of minute virus of mice P4 promoter-generated pre-mRNA caused a decrease in the accumulated levels of P4-generated R2 mRNA relative to P4-generated R1 mRNA, although the total accumulated levels of P4 product remained the same. This effect was seen in nuclear RNA and was independent of RNA stability. The 5' and 3' elements of the bipartite NS2-specific exon enhancer are redundant in function, and when the 2018 PTC was combined with a deletion of the 3' enhancer element, the exon was skipped in the majority of the viral P4-generated product. Such exon skipping in response to a PTC, but not a missense mutation at nt 2018, could be suppressed by frame shift mutations in either exon of NS2 which reopened the NS2 open reading frame, as well as by improvement of the upstream intron 3' splice site. These results suggest that a PTC can interfere with the function of an exon splicing enhancer in an open reading frame-dependent manner and that the PTC is recognized in the nucleus.  (+info)

Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. (4/7062)

Splicing enhancers are RNA sequences required for accurate splice site recognition and the control of alternative splicing. In this study, we used an in vitro selection procedure to identify and characterize novel RNA sequences capable of functioning as pre-mRNA splicing enhancers. Randomized 18-nucleotide RNA sequences were inserted downstream from a Drosophila doublesex pre-mRNA enhancer-dependent splicing substrate. Functional splicing enhancers were then selected by multiple rounds of in vitro splicing in nuclear extracts, reverse transcription, and selective PCR amplification of the spliced products. Characterization of the selected splicing enhancers revealed a highly heterogeneous population of sequences, but we identified six classes of recurring degenerate sequence motifs five to seven nucleotides in length including novel splicing enhancer sequence motifs. Analysis of selected splicing enhancer elements and other enhancers in S100 complementation assays led to the identification of individual enhancers capable of being activated by specific serine/arginine (SR)-rich splicing factors (SC35, 9G8, and SF2/ASF). In addition, a potent splicing enhancer sequence isolated in the selection specifically binds a 20-kDa SR protein. This enhancer sequence has a high level of sequence homology with a recently identified RNA-protein adduct that can be immunoprecipitated with an SRp20-specific antibody. We conclude that distinct classes of selected enhancers are activated by specific SR proteins, but there is considerable sequence degeneracy within each class. The results presented here, in conjunction with previous studies, reveal a remarkably broad spectrum of RNA sequences capable of binding specific SR proteins and/or functioning as SR-specific splicing enhancers.  (+info)

A new element within the T-cell receptor alpha locus required for tissue-specific locus control region activity. (5/7062)

Locus control regions (LCRs) are cis-acting regulatory elements thought to provide a tissue-specific open chromatin domain for genes to which they are linked. The gene for T-cell receptor alpha chain (TCRalpha) is exclusively expressed in T cells, and the chromatin at its locus displays differentially open configurations in expressing and nonexpressing tissues. Mouse TCRalpha exists in a complex locus containing three differentially regulated genes. We previously described an LCR in this locus that confers T-lineage-specific expression upon linked transgenes. The 3' portion of this LCR contains an unrestricted chromatin opening activity while the 5' portion contains elements restricting this activity to T cells. This tissue-specificity region contains four known DNase I hypersensitive sites, two located near transcriptional silencers, one at the TCRalpha enhancer, and another located 3' of the enhancer in a 1-kb region of unknown function. Analysis of this region using transgenic mice reveals that the silencer regions contribute negligibly to LCR activity. While the enhancer is required for complete LCR function, its removal has surprisingly little effect on chromatin structure or expression outside the thymus. Rather, the region 3' of the enhancer appears responsible for the tissue-differential chromatin configurations observed at the TCRalpha locus. This region, herein termed the "HS1' element," also increases lymphoid transgene expression while suppressing ectopic transgene activity. Thus, this previously undescribed element is an integral part of the TCRalphaLCR, which influences tissue-specific chromatin structure and gene expression.  (+info)

The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and cyclic-AMP-dependent transcription. (6/7062)

The gene encoding the Na/I symporter (NIS) is expressed at high levels only in thyroid follicular cells, where its expression is regulated by the thyroid-stimulating hormone via the second messenger, cyclic AMP (cAMP). In this study, we demonstrate the presence of an enhancer that is located between nucleotides -2264 and -2495 in the 5'-flanking region of the NIS gene and that recapitulates the most relevant aspects of NIS regulation. When fused to either its own or a heterologous promoter, the NIS upstream enhancer, which we call NUE, stimulates transcription in a thyroid-specific and cAMP-dependent manner. The activity of NUE depends on the four most relevant sites, identified by mutational analysis. The thyroid-specific transcription factor Pax8 binds at two of these sites. Mutations that interfere with Pax8 binding also decrease transcriptional activity of the NUE. Furthermore, expression of Pax8 in nonthyroid cells results in transcriptional activation of NUE, strongly suggesting that the paired-domain protein Pax8 plays an important role in NUE activity. The NUE responds to cAMP in both protein kinase A-dependent and -independent manners, indicating that this enhancer could represent a novel type of cAMP responsive element. Such a cAMP response requires Pax8 but also depends on the integrity of a cAMP responsive element (CRE)-like sequence, thus suggesting a functional interaction between Pax8 and factors binding at the CRE-like site.  (+info)

Reduced phosphorylation of p50 is responsible for diminished NF-kappaB binding to the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells. (7/7062)

Reduced cell surface levels of major histocompatibility complex class I antigens enable adenovirus type 12 (Ad12)-transformed cells to escape immunosurveillance by cytotoxic T lymphocytes (CTL), contributing to their tumorigenic potential. In contrast, nontumorigenic Ad5-transformed cells harbor significant cell surface levels of class I antigens and are susceptible to CTL lysis. Ad12 E1A mediates down-regulation of class I transcription by increasing COUP-TF repressor binding and decreasing NF-kappaB activator binding to the class I enhancer. The mechanism underlying the decreased binding of nuclear NF-kappaB in Ad12-transformed cells was investigated. Electrophoretic mobility shift assay analysis of hybrid NF-kappaB dimers reconstituted from denatured and renatured p50 and p65 subunits from Ad12- and Ad5-transformed cell nuclear extracts demonstrated that p50, and not p65, is responsible for the decreased ability of NF-kappaB to bind to DNA in Ad12-transformed cells. Hypophosphorylation of p50 was found to correlate with restricted binding of NF-kappaB to DNA in Ad12-transformed cells. The importance of phosphorylation of p50 for NF-kappaB binding was further demonstrated by showing that an NF-kappaB dimer composed of p65 and alkaline phosphatase-treated p50 from Ad5-transformed cell nuclear extracts could not bind to DNA. These results suggest that phosphorylation of p50 is a key step in the nuclear regulation of NF-kappaB in adenovirus-transformed cells.  (+info)

Contributions to gene activation by multiple functions of Bicoid. (8/7062)

Bicoid is a Drosophila morphogenetic protein required for the development of anterior structures in the embryo. To gain a better understanding of how Bicoid works as a transcriptional activator, we systematically analysed various functions of Bicoid required for gene activation. We provide evidence suggesting that Bicoid is an intrinsically weak activator. First, our biochemical experiments demonstrate that the Bicoid-DNA complexes are very unstable, suggesting a weak DNA-binding function of Bicoid. This idea is further supported by our experiments demonstrating that the same number of LexA-Bicoid fusion molecules can activate transcription more effectively from LexA sites than from Bicoid sites. Secondly, we demonstrate that transcriptional activation by the weak activator Bicoid is readily influenced by the local enhancer environment. These influences are decreased when the Bicoid function is enforced by attaching to it either a known dimerization domain or the strong activation domain VP16. VP16 can also compensate for the loss of some Bicoid sites in an enhancer element. Our experiments demonstrate that the outcome of transcriptional activation by Bicoid is determined by multiple weak functions that are interconnected, a finding that can further help us to understand how this morphogenetic protein achieves its molecular functions.  (+info)

We analyzed the contribution of DRMs and other short DNA sequence motifs to the activity patterns of human enhancers across hundreds of cellular contexts. In contrast to the model proposed in Drosophila [16], GC DRMs were enriched in broadly active enhancers compared to both the genomic background and context-specific enhancers, while TA DRMs were depleted. Using an unbiased machine learning framework, we found that DRM occurrence patterns were only weakly predictive of broadly active human enhancers (ROC AUC ranging from 0.55 to 0.61). However, a classifier trained on the occurrence of all possible 6-bp sequences very accurately distinguished broadly active human enhancers from the genomic background (ROC AUC = 0.93), GC-matched background regions (ROC AUC = 0.87), and context-specific enhancers (ROC AUC = 0.87). Furthermore, 6-mers highly predictive of broad activity tended to be GC-rich, while those with the most negative weights tended to be GC-poor, even when classifying GC-matched regions. ...
Mapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identify cis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors. Several KLFs have been demonstrated to play important roles in hematopoiesis. However, transcriptional regulation of KLFs via CREs, particularly enhancers, in erythroid cells has been poorly understood. In this study, 23 erythroid-specific or putative erythroid-specific DHSs were identified by DNase-seq in the genomic regions of 17 human KLFs, and their enhancer activities were evaluated using dual-luciferase reporter (DLR) assay. Of the 23 erythroid-specific DHSs, the enhancer activities of 15 DHSs were comparable to that of the classical enhancer HS2 in driving minimal promoter (minP). Fifteen DHSs, some overlapping those that increased minP activities, acted as enhancers when driving the corresponding
In this study, tissue-specific enhancers (and promoters) were identified based on the presence of H3K27ac and absence of H3K4me3. Most previous studies in Drosophila have used the binding pattern of known cardiogenic TFs to identify cardiac-specific enhancers genome-wide (Jin et al., 2013; Junion et al., 2012). However, this approach can only be applied to well-characterized TFs with a known role in the tissue of interest, and for which an antibody is available. ChIP against TFs will also only identify a subset of the enhancers involved, unless a clear master regulator of that tissues development is known. By contrast, H3K27ac is thought to unravel functionally active enhancers (Bonn et al., 2012b) without any prior knowledge of the TFs involved.. In this study, we show that presence of the H3K27ac mark is not an absolute predictor of tissue-specific activity, as even in purified population of cardiac nuclei only ∼60% of identified active enhancers drive expression in this cell type. Although ...
Potential enhancer elements are enriched for p300 binding, and their target genes are highly bound by Pol II. (a) P300 binding site enrichment in CEEs. (b) Pol
TY - JOUR. T1 - HS2 enhancer function is blocked by a transcriptional terminator inserted between the enhancer and the promoter. AU - Ling, Jianhua. AU - Ainol, Lincoyan. AU - Zhang, Ling. AU - Yu, Xiuping. AU - Pi, Wenhu. AU - Tuan Lo, Dorothy. PY - 2004/12/3. Y1 - 2004/12/3. N2 - The HS2 enhancer in the β-globin locus control region regulates transcription of the globin genes 10-50 kb away. How the HS2 enhancer acts over this distance is not clearly understood. Earlier studies show that in erythroid cells the HS2 enhancer initiates synthesis of intergenic RNAs from sites within and downstream of the enhancer, and the enhancer-initiated RNAs are transcribed through the intervening DNA into the cis-linked promoter and gene. To investigate the functional significance of the enhancer-initiated transcription, here we inserted the lac operator sequence in the intervening DNA between the HS2 enhancer and the eglobin promoter in reporter plasmids and integrated the plasmids into erythroid K562 cells ...
The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA-2 physiological activities necessitate that it be strictly regulated, and cell type-specific enhancers fulfill this role. The +9.5 intronic enhancer harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic in humans. Since mechanisms underlying how GATA2 enhancer disease mutations impact hematopoiesis and pathology are unclear, we generated mouse models of the enhancer mutations. While a multi-motif mutant was embryonically lethal, a single-nucleotide Ets motif mutant was viable, and steady-state hematopoiesis was normal. However, the Ets motif mutation abrogated stem/progenitor cell regeneration following stress. These results reveal a new mechanism in human genetics, in which a disease ...
The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA-2 physiological activities necessitate that it be strictly regulated, and cell type-specific enhancers fulfill this role. The +9.5 intronic enhancer harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic in humans. Since mechanisms underlying how GATA2 enhancer disease mutations impact hematopoiesis and pathology are unclear, we generated mouse models of the enhancer mutations. While a multi-motif mutant was embryonically lethal, a single-nucleotide Ets motif mutant was viable, and steady-state hematopoiesis was normal. However, the Ets motif mutation abrogated stem/progenitor cell regeneration following stress. These results reveal a new mechanism in human genetics, in which a disease ...
TY - JOUR. T1 - Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis. AU - Glasgow, Stacey M.. AU - Carlson, Jeffrey C.. AU - Zhu, Wenyi. AU - Chaboub, Lesley S.. AU - Kang, Peng. AU - Lee, Hyun Kyoung. AU - Clovis, Yoanne M.. AU - Lozzi, Brittney E.. AU - McEvilly, Robert J.. AU - Rosenfeld, Michael G.. AU - Creighton, Chad J.. AU - Lee, Soo-Kyung. AU - Mohila, Carrie A.. AU - Deneen, Benjamin. PY - 2017. Y1 - 2017. N2 - Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial ...
Various enhancer lengths and compositions result in similar levels of virus propagation.To characterize the synthetic enhancer sequences acquired by enhancerless SV40, viral DNA was isolated from cell lysates and subcloned. After a sequencing step, selected clones were reanalyzed by retransfecting cells to identify opportunistic genomes, which had replicated without having incorporated a functional enhancer of their own. In the case of HCMV oligonucleotides, we found all four enhancer motifs in various combinations and orientations in different isolates (Fig. 1C), which upon retesting were similarly infective (first signs of cytopathic effects [CPE] at around day 10 and full infection at around day 14 after transfection). Thus, although the lengths and compositions of the isolated enhancers were quite variable, our experimental setup apparently selected for viral enhancers with similar activities. Of note, the 18-bp repeat, which harbors a previously described binding site for NF-κB (23), was ...
Transcription factor binding to enhancer elements is critical for proper gene regulation. Enhancers are often found in noncoding sequences in close proximity to the gene that they regulate and sometimes even on another chromosome; however, whether they are also found in exons, the coding regions of DNA, is unclear. Birnbaum et al. analyzed 25 mouse and human enhancer-associated ChIP-seq data sets in order to identify enhancer peaks that overlap exons and found regulatory transcription factor binding to exonic regions. In fact, in mice, roughly 7% of enhancer peaks overlapped coding exons. Mutation of these elements in zebrafish and mouse enhancer assays showed that although exonic sequences are necessary, they are not sufficient for full enhancer function. Absence of an exon-encoded enhancer, however, did have functional consequences. Thus, exonic sequences may function in the regulation of nearby genes. Moreover, phenotypes seen in genetic knockout animals may be the result of not only the lack ...
The Drosophila pan-neural genes deadpan (dpn) and scratch (scrt) are expressed in most or all developing neural precursor cells of the central nervous system (CNS) and peripheral nervous system (PNS). We have identified a cis-acting enhancer element driving full pan-neural expression of the dpn gene which is composed of independent CNS- and PNS-specific subelements. We have also identified CNS- and PNS-specific subelements of the scrt enhancer. Deletion analysis of the dpn and scrt PNS-specific subelements reveals that PNS specificity of these two evolutionarily unrelated enhancers is achieved in part by repression of CNS expression. We discuss the implications of the striking organizational similarities of the dpn, scrt, and sna pan-neural enhancers.. ...
Author(s): Bothma, Jacques P; Garcia, Hernan G; Ng, Samuel; Perry, Michael W; Gregor, Thomas; Levine, Michael | Abstract: Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hunchback, and snail-in developing Drosophila embryos. The knirps enhancers exhibit additive, sometimes even super-additive activities, consistent with classical gene fusion studies. In contrast, the hunchback enhancers function sub-additively in anterior regions containing saturating levels of the Bicoid activator, but function additively in regions where there are diminishing levels of the Bicoid gradient. Strikingly sub-additive behavior is also observed for snail, whereby removal of the proximal enhancer causes a significant increase in gene expression. Quantitative
However, a limitation of this approach is the requirement of genomic libraries in any sequenced species in order to test regions of interest for regulatory activity. Furthermore, the sizes of these libraries need to be relatively small (~20 kb) for efficient integration into the genome using the phiC31 integrase system.. The investment required to generate such libraries is estimably large and could pose a signficant hurdle for use of such an application.. Another caveat is that positive clones need to be further characterized to identify the minimal enhancer fragment(s).. This method also does not inform us of the presence of multiple enhancers in a clone that is being tested.. Nevertheless, for those species where this method is feasible, complementing this assay with computational enhancer discovery methods and/or epigenetic/chromatin profiling methods to zero in on the minimal regulatory regions will greatly aid in the rapid identification and annotation of these critical components of the ...
Looking for enhancer sequence? Find out information about enhancer sequence. in mathematics, ordered set of mathematical quantities called terms. A sequence is said to be known if a formula can be given for any particular term using... Explanation of enhancer sequence
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Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation. ...
Author(s): Perry, Michael W. | Advisor(s): Levine, Michael; Patel, Nipam | Abstract: Modification of cis-regulatory sequences is an important means by which developmental processes can evolve and generate changes in patterning and morphology. Understanding how these cis-regulatory enhancer sequences control gene expression is critical not only for understanding the mechanistic basis of development, but also for understanding how the systems are modified or evolve over time. In this work I describe the discovery and characterization of many new enhancers that regulate genes for which a similar enhancer driving a similar expression pattern was previously known; these are shadow enhancers. The genes examined are critical developmental control genes responsible for the patterning and subdivision of the early Drosophila embryo. At first glance, many of these enhancers seem redundant, but are found to be evolutionarily conserved, suggesting a role in fitness and specific developmental function.
We have leveraged chromatin profiling and a novel analytic approach to identify genomic rearrangements associated with active enhancers, revealing both known enhancer hijacking events as well as novel enhancer duplications of likely oncogenic significance in lymphoma. Our focused investigation of two recurrently altered loci, MYC and BCL6, in the presence and absence of rearrangements and across multiple lymphoma subtypes, provided novel insights about the role of native and rearranged enhancers in controlling these critical oncogenes. Understanding such mechanisms may be of particular clinical significance, given the ongoing development of drugs that target enhancer function (42). Moreover, we believe that the efficient PEAR-ChIP approach described here expands future possibilities for identification of enhancer-associated rearrangements in research or clinical settings.. PEAR-ChIP efficiently detected genomic rearrangements in lymphoma samples, despite the fact that our datasets cover only a ...
The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities ...
Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR). This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220) that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in non-protein coding regions as it emerges from ...
1. Hong J-W, Hendrix DA, Levine MS. Shadow enhancers as a source of evolutionary novelty. Science. 2008;321: 1314. doi: 10.1126/science.1160631 18772429. 2. Wunderlich Z, Bragdon MDJ, Vincent BJ, White JA, Estrada J, DePace AH. Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers. Cell Rep. 2016;14: 3030. doi: 10.1016/j.celrep.2016.03.032 27028762. 3. Perry MW, Boettiger AN, Bothma JP, Levine M. Shadow enhancers foster robustness of Drosophila gastrulation. Curr Biol. 2010;20: 1562-1567. doi: 10.1016/j.cub.2010.07.043 20797865. 4. Frankel N, Davis GK, Vargas D, Wang S, Payre F, Stern DL. Phenotypic robustness conferred by apparently redundant transcriptional enhancers. Nature. 2010;466: 490-493. doi: 10.1038/nature09158 20512118. 5. Osterwalder M, Barozzi I, Tissières V, Fukuda-Yuzawa Y, Mannion BJ, Afzal SY, et al. Enhancer redundancy provides phenotypic robustness in mammalian development. Nature. 2018;554: 239-243. doi: 10.1038/nature25461 ...
By contrast, the active regulatory elements identified by WHG-STARR-seq that are located in closed chromatin regions active and closed enhancers are not associated with DNase I signal,
MLL4 (KMT2D) is a major mammalian H3K4 mono- and di-methyltransferase that is essential for enhancer activation, cell-type-specific gene expression, and cell differentiation.
Fingerprint Dive into the research topics of A Mathematical Model for Enhancer Activation Kinetics During Cell Differentiation. Together they form a unique fingerprint. ...
Several lines of work suggest that the 3′ enhancer region would control CSR. Chromatin interactions between heavy chain genes and HS1,2 suggest functional interactions (Wuerffel et al., 2007). Deletions or replacements of individual hypersensitive regions (Cogné et al., 1994; Manis et al., 1998; Seidl et al., 1999) implicate the 3′ regulatory locus in CSR. Additionally, insertions of foreign sequence in the locus also affect CSR, possibly by disrupting interactions between enhancer elements (Seidl et al., 1999). However, any conclusions are complicated by the fact that clean deletion of single elements reveals only a minimal phenotype (Manis et al., 1998; Seidl et al., 1999; Vincent-Fabert et al., 2009). Deletion of both HS3B and HS4 (Pinaud et al., 2001) from the germline demonstrates a role in CSR to some heavy chain genes. To pursue the role of the 3′ enhancer region, over the last 10 yr, several laboratories have attempted to delete all four elements from the mouse germline, but for ...
It remains unclear how a limited amount of maternal transcription factor Dorsal (Dl) directs broad expression of short gastrulation (sog) throughout the presumptive neurogenic ectoderm in the Drosophila early embryo. Here, we present evidence that the sog shadow enhancer employs dual modes of transcriptional synergy to produce this broad pattern. Bioinformatics analyses indicated that a minimal enhancer region, systematically mapped in vivo, contains five Dl-, three Zelda (Zld)-, and three Bicoid (Bcd)-binding sites; four of these five Dl-binding sites are closed linked to two Zld- and two Bcd-binding sites. Mutations of either the linked Zld- or Bcd-binding sites led to severe reduction in lacZ expression width, length, and/or strength in transgenic embryos. In addition, alteration of the helical phasing in this enhancer region by insertion of spacer sequences between linked sites also resulted in aberrant lacZ expression. These results suggest that synergistic interactions between Dl and Zld and
Contents of the 15 Chapter for This Feed Palatabilty Enhancers Market Study:-. Chapter 1: to describe Global Feed Palatabilty Enhancers Market Introduction, product scope, market overview, market opportunities, market risk, market driving force;. Chapter 2: to analyze the top manufacturers of Global Feed Palatabilty Enhancers Market, with sales, revenue, and price of Global Feed Palatabilty Enhancers Market, in 2016 and 2017;. Chapter 3: to display the competitive situation among the top manufacturers, with sales, revenue and market share in 2016 and 2017;. Chapter 4: to show the Global Feed Palatabilty Enhancers market by regions, with sales, revenue and market share of Global Feed Palatabilty Enhancers Market, for each region, from 2012 to 2017;. Chapter 5, 6, 7, 8 and 9: to analyze the key regions, with sales, revenue and market share by key countries in these regions;. Chapter 10 and 11: to show the market by type and application, with sales market share and growth rate by type, application, ...
Human blood monocytes comprise at least 3 subpopulations that differ in phenotype and function. Here, we present the first in-depth regulome analysis of human classical (CD14++CD16-), intermediate (CD14+CD16+), and nonclassical (CD14dimCD16+) monocytes. Cap analysis of gene expression adapted to Helicos single-molecule sequencing was used to map transcription start sites throughout the genome in all 3 subsets. In addition, global maps of H3K4me1 and H3K27ac deposition were generated for classical and nonclassical monocytes defining enhanceosomes of the 2 major subsets. We identified differential regulatory elements (including promoters and putative enhancers) that were associated with subset-specific motif signatures corresponding to different transcription factor activities and exemplarily validated novel downstream enhancer elements at the CD14 locus. In addition to known subset-specific features, pathway analysis revealed marked differences in metabolic gene signatures. Whereas classical ...
CD4+CD25+FOXP3+ human regulatory T cells (Tregs) are essential for self-tolerance and immune homeostasis. Here, we describe the promoterome of CD4+CD25highCD45RA+ naïve and CD4+CD25highCD45RA-memory Tregs and their CD25- conventional T-cell (Tconv) counterparts both before and after in vitro expansion by cap analysis of gene expression (CAGE) adapted to single-molecule sequencing (HeliScopeCAGE). We performed comprehensive comparative digital gene expression analyses and revealed novel transcription start sites, of which several were validated as alternative promoters of known genes. For all in vitro expanded subsets, we additionally generated global maps of poised and active enhancer elements marked by histone H3 lysine 4 monomethylation and histone H3 lysine 27 acetylation, describe their cell type-specific motif signatures, and evaluate the role of candidate transcription factors STAT5, FOXP3, RUNX1, and ETS1 in both Treg- and Tconv-specific enhancer architectures. Network analyses of gene ...
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The generation of distinctive cell types that form different tissues and organs requires precise, temporal and spatial control of gene expression. This depends on specific cis-regulatory elements distributed in the non-coding DNA surrounding their target genes. Studies performed on mammalian embryonic stem cells and Drosophila embryos suggest that active enhancers form part of a defined chromatin landscape marked by histone H3 lysine 4 mono-methylation (H3K4me1) and histone H3 lysine 27 acetylation (H3K27ac). Nevertheless, little is known about the dynamics and the potential roles of these marks during vertebrate embryogenesis. Here we provide genomic maps of H3K4me1/me3 and H3K27ac at four developmental time-points of zebrafish embryogenesis and analyze embryonic enhancer activity. We find that: (i) changes in H3K27ac enrichment at enhancers accompany the shift from pluripotency to tissue-specific gene expression; (ii) in early embryos, the peaks of H3K27ac enrichment are bound by pluripotent ...
The Cd4 Proximal Enhancer Inhibits Cd4-Cd8 Association(A) Flow cytometry analysis of wild-type and Cd4 PE-deficient thymocytes (Cd4 PE Δ/Δ).(B) Cd4-Cd8 associ
The deep understanding on the transcription regulation in variety of organs and tissues is required to establish and optimize the protocols for cell/organ induction in vitro. It is known that the genomic element called enhancer has important roles in transcriptional regulation within each tissue/organ. However, the mechanisms how an enhancer activates some repressed gene promoter remain elusive. In our proposed study, we will clarify the dual step mechanisms how an enhancer interacts to repressed promoter and how an enhancer liberates the promoter from repression. We further inspect and pursue whether such interaction can be proper indication for sound differentiation and induction of tissue/organ in vitro.. ...
Chromatin Flags Active Enhancers. Modifications to histone proteins (green and red dots) mark active enhancers, where a transcription complex (colored circles) assembles on a chromosome. DNA then loops over (arrow) to contact an active promoter (gray rectangle) and initiate transcription. [Courtesy of Calo and Wysocka, 2013.] In the case of myeloid cells, the new genes primarily relate to the endolysosomal system, highlighting the idea that the risk for Alzheimers may depend on how effectively microglia respond to amyloid and brain damage and clean up debris (Apr 2019 conference news). This study is an important step toward extracting meaningful biology from genomic studies of Alzheimers disease. The prioritization of variants and genes will accelerate the generation of disease-relevant models, ultimately leading to a better understanding of pathogenesis, Matthew Hill at Cardiff University, U.K., wrote to Alzforum (full comment below).. Goate and colleagues became interested in the ...
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A recent paper conducted a tour de force of anatomy, tracing every single neuron going to and from the mushroom body. The technique they used to do this is interesting in itself, called an enhancer trap. Fly researchers have been generating a vast number of lines, or inbred fly mutants, by inserting a two bits of DNA from yeast cells. The first is the gene encoding a transcription activator, GAL4. This is induced to jump randomly in the fly genome, hoping that lands downstream of the regulatory region of an endogenous gene, i.e. its enhancer or promoter. The second bit is a binding site for this GAL4 protein, linked to a gene that expresses some useful marker, typically a fluorescent protein like GFP. Since the yeast GAL4 protein works just fine to activate RNA transcription and gene expression in flies, the end result is that GFP gets expressed in reponse to a single enhancer somewhere else in the genome. Indeed researchers try to saturate the genome, generating a huge number of lines ...
Eukaryotic gene expression is mediated by compact cis-regulatory modules, or enhancers, which are bound by specific sets of transcription factors. The combinatorial interaction of these bound transcription factors determines time- and tissue-specific gene activation or repression. The even-skipped s …
OBJECTIVE: Genetic variants in the region of tumor necrosis factor-induced protein 3-interacting protein 1 (TNIP1) are associated with autoimmune disease and reduced TNIP1 gene expression. The aim of this study was to define the functional genetic mechanisms driving TNIP1 hypomorphic expression imparted by the systemic lupus erythematosus-associated TNIP1 H1 risk haplotype. METHODS: Dual luciferase expression and electrophoretic mobility shift assays were used to evaluate the allelic effects of 11 risk variants on enhancer function and nuclear protein binding in immune cell line models (Epstein-Barr virus [EBV]-transformed human B cells, Jurkat cells, and THP-1 cells), left in a resting state or stimulated with phorbol 12-myristate 13-acetate/ionomycin. HiChIP was used to define the regulatory 3-dimensional (3-D) chromatin network of the TNIP1 haplotype by detecting in situ long-range DNA contacts associated with H3K27ac-marked chromatin in EBV B cells. Then, quantitative reverse ...
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The Pathway Profiling Systems provide a means to assess signal transduction pathway activation in vivo. These systems consist of sets of vectors that each contain a distinct cis-acting enhancer element upstream of a reporter gene.
The Pathway Profiling Systems provide a means to assess signal transduction pathway activation in vivo. These systems consist of sets of vectors that each contain a distinct cis-acting enhancer element upstream of a reporter gene.
Although it has been assumed that the deregulated bcl-2 expression in t(14;18) cells is mediated in part by the immunoglobulin heavy chain gene regulatory region, this has not been demonstrated, nor was it known which elements of that region were responsible for the deregulation. In these studies, we found that the four DNase I-hypersensitive regions within the IgH 3′ enhancer were able to activate the bcl-2 promoter in the t(14;18) cell line DHL-4. Of those four hypersensitive regions, we demonstrated that HS4 had the most influence on bcl-2 promoter activity. This is similar to the situation in pre-B and plasmacytoma cells, where HS4 is the most active enhancer region. We also showed that the HS1,2 region was capable of activating the promoter independently. By itself, HS3 increased bcl-2 promoter activity by only a minor amount. Other studies of HS3 have shown that it is contains elements that act as negative effectors of the IgH 3′ enhancer (37) , and preliminary studies in our ...
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Pioneer Award funded research in the laboratory of Dr. Ramin Shiekhattar, a leader in epigenetics and RNA biology fields, is centered on identifying mechanisms and factors involved in enhancer function and enhancer deregulation in pancreatic cancer and melanoma using novel tools and methods toward enhancer therapy in cancer. These will include dissecting the role of enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) in enhancer function and cancer progression.. Successful applicants will work on projects aimed at identifying and verifying the function of enhancer regulatory proteins and other epigenetic factors, during pancreatic and skin cancer progression. The group is using state-of-the-art techniques and model systems to achieve these goals, including protein loss-of-function (shRNA, CRISPR/Cas9), proteomic analysis (mass-spectrometry), and global genomics and transcriptomics technologies (RNA-seq, ChIP-seq) in cancer cell lines and patient-derived xenograft tumor ...
TY - JOUR. T1 - The human λ immunoglobulin enhancer is controlled by both positive elements and developmentally regulated negative elements. AU - Glozak, Michele A.. AU - Blomberg, Bonnie B.. N1 - Funding Information: Acknowledgements-We thank Drs Tucker LeBien and Max Cooper for pre-B lines, including the acutel ymphoblasticc ell line 697 and Drs James Hagman and Ursula Storb for the OPXZAT construct.W e appreciateM ary Donohoe and Drs Ursula Storb, CharlesE isenbeis,a nd Harinder Singh for reading and commentingo n the manuscript.T his work was supported by the National Instituteso f Health grant AI21870 to B. Blomberg.. PY - 1996. Y1 - 1996. N2 - We have recently reported the localization of the first transcriptional enhancer in the human lambda (λ) immunoglobulin light chain locus. Enhancer activity was contained on a 1.2 kb SstI fragment, with partial activity retained on a core 111 bp PstI-SstI fragment. This enhancer is located 11.7kb downstream of Cλ7, the most 3 lambda constant ...
When the gypsy retrotransposon of Drosophila inserts between an enhancer and promoter it prevents the enhancer from activating transcription. Enhancers are blocked because the protein (SUHW) encoded by the suppressor of Hairy-wing [su(Hw)] gene binds to gypsy. For example, gypsy insertions in an 85 kilobase region between a wing margin-specific enhancer and the promoter in the cut gene cause a cut wing phenotype that is suppressed by su(Hw) mutations. A temperature-sensitive combination of mutant su(Hw) alleles was used to investigate the mechanism by which SUHW blocks the cut wing margin enhancer. By shifting from the nonpermissive to the permissive temperature and vice versa at various stages in development it was found that active SUHW is only required around pupariation when the wing margin enhancer is active to cause a cut wing phenotype. This was true whether gypsy was in the embryonic control region near the promoter, or in the late larval control region near the wing margin enhancer. ...
Stem cells are a central feature of metazoan biology. Haematopoietic stem cells (HSCs) represent the best-characterized example of this phenomenon, but the molecular mechanisms responsible for their formation remain obscure. The stem cell leukaemia (SCL) gene encodes a basic helix-loop-helix (bHLH) transcription factor with an essential role in specifying HSCs. Here we have addressed the transcriptional hierarchy responsible for HSC formation by characterizing an SCL 3 enhancer that targets expression to HSCs and endothelium and their bipotential precursors, the haemangioblast. We have identified three critical motifs, which are essential for enhancer function and bind GATA-2, Fli-1 and Elf-1 in vivo. Our results suggest that these transcription factors are key components of an enhanceosome responsible for activating SCL transcription and establishing the transcriptional programme required for HSC formation.
The transcription factor p63 plays a pivotal role in keratinocyte proliferation and differentiation in the epidermis. However, how p63 regulates epidermal genes during differentiation is not yet clear. Using epigenome profiling of differentiating human primary epidermal keratinocytes, we characterized a catalog of dynamically regulated genes and p63-bound regulatory elements that are relevant for epithelial development and related diseases. p63-bound regulatory elements occur as single or clustered enhancers, and remarkably, only a subset is active as defined by the co-presence of the active enhancer mark histone modification H3K27ac in epidermal keratinocytes. We show that the dynamics of gene expression correlates with the activity of p63-bound enhancers rather than with p63 binding itself. The activity of p63-bound enhancers is likely determined by other transcription factors that cooperate with p63. Our data show that inactive p63-bound enhancers in epidermal keratinocytes may be active ...
Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication. Academic Article ...
OBJECTIVE: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3 enhancer complex regulatory region (IgH3EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations. METHODS: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes. RESULTS: The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of allele *2 in the SSc cohort highly significant versus controls (57% vs. 40%, p,0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients ...
We have examined the interaction of factors in HeLa cell nuclear extracts with a human histone H2B gene (H2B) promoter. Protein-DNA mobility-shift and DNase I protection assays detected a factor(s) binding to a 15-base-pair consensus element that is essential for efficient H2B transcription in vitro. Part of this consensus sequence is the octanucleotide ATTTGCAT, which is apparently a functional component of several non-histone genes. A subset of these genes, including a human U2 small nuclear RNA (snRNA) gene promoter, a mouse immunoglobulin heavy chain enhancer, and a mouse light chain promoter, were shown to interact with the H2B consensus sequence-binding factor(s). These results suggest that a common factor or closely related factors may contribute to the regulation of these and other genes that share the octanucleotide sequence.. ...
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High-throughput interaction data from novel chromosome interaction assays has become a staple in genomics research. Methods such as high-throughput chromosome conformation capture (Hi-C) and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) provide researchers with a way of quantifying three-dimensional chromatin architecture, while also gaining insights into which regions in the genome are interacting frequently. A common downstream data-type from these experimental methods is chromatin loop data. Loops are inferred by marking regions in the genome with high frequency of interaction compared to a background. Typically, we are interested in loops because they provide an insulated environment for interaction of genomic regions, as well as a direct mode of contact for regions near the loop anchors. A classic canonical chromatin loop interaction is one that involves enhancer-promoter interactions in the regulation of gene expression. Therefore, a very common workflow involving ...
Pioneer factors play a critical role in differentiation by generating chromatin accessibility and by activating enhancers. As differentiation progress, additional tissue-specific transcription factors bind these enhancers thus generating a stable and robust regulatory network that is thought to be resistant to the loss of any specific transcription factor. I found that pioneer factors are continuously guarding enhancer activity throughout adult life thus maintaining tissue integrity. An exception to this is DNA hypomethylation at these sites that are programmed by pioneer factors in embryonic development and are not dependent on the continuous presence of pioneer factors in the adult tissue. These findings distinguish between cellular components that enhance stability versus those that enable plasticity.. Abstract. ...
Abnormal epigenetic marking is well documented in gene promoters of cancer cells, but the study of distal regulatory siteshas lagged behind.We performed a systematic analysis of DNA methylation sites connected with gene expression profilesacross normal and cancerous human genomes. Utilizing methylation and expression data in 58 cell types, we developed a model for methylation-expression relationships in gene promoters and extrapolated it to the genome. We mapped numerous sites at which DNA methylation was associated with expression of distal genes. These sites bind transcription factors in a methylation-dependent manner, and carry the chromatin marks of a particular class of transcriptional enhancers. In contrast to the traditional model of one enhancer site per cell type, we found that single enhancer sites may define gradients of expression levels across many different cell types. Strikingly, the identified sites were drastically altered in cancers: hypomethylated enhancer sites associated with
Mens Princess Yumian also stayed in Bulge a daze Two women, one Mens Bulge Enhancer Penis Cup Pouch heroic and one Penis Enhancer gentle, were unexpectedly persistent Cup and firm when Pouch looking for a man Their eyes smashed into the air with an electric spark. Mens but now suddenly full of expectations Bulge When everyone was talking Enhancer Penis here, suddenly Cup saw a somersault cloud flying from the Pouch sky, and Mens Bulge Enhancer Mens Bulge Enhancer Penis Cup Pouch Penis Cup Pouch Sun Wukong came back. It is used by body builders to increase muscle strength during training It is a non essential protein, which provides its phosphate to ATP Adenosine triphosphate. Of course, Fang Senyans decision is not unquestionable For example, Paul told Fang Senyan after some calculations We have almost mastered Mens Bulge Enhancer Penis Cup Pouch the basic data of the grumpy beast The health value of the ordinary grumpy beast is usually 800 Click this position, their defense power is usually 10 ...
In Ad12 tumorigenic cells, surface levels of the major histocompatibility class I antigens become greatly diminished, enabling these cancerous cells to escape immunosurveillance by cytotoxic T lymphocytes. Weve shown that the E1A-12 protein mediates this effect by altering the binding of two transcription factors (NF-kB and COUP-TF) to the class I enhancer which, in turn, blocks transcription from the class I promoter. Specifically, the activator NF-kB becomes hypophosphorylated on a specific residue (serine 337) that disables it from binding to its cognate recognition site on the class I enhancer. This finding alone provided a new dimension into how NF-kB, the major regulator of genes involved in immune defense, can modulate gene expression. In addition, the repressor COUP-TF becomes strongly bound to a different recognition site on the class I enhancer, where it associates with a histone deacetylase (HDAC) and E1A-12, resulting in chromatin compaction. In this way, E1A-12 mediates global ...
Anyone living with asthma can testify that this respiratory condition may be agitated by almost anything - be it common allergens like pollen or too much physical exertion. Many people rely on inhalers to manage their symptoms, which include coughing fits that make it difficult to fully take in air. However, new research has revealed that a well-known brain enhancer may be able to counter these attacks as well, and could even reduce the need for more powerful medications.. According to a press release from ScienceDaily, researchers from Indiana University have discovered that an omega-3 fatty acid supplement derived from a specific mussel found off the coast of New Zealand could potentially provide relief for people with asthma who experience airway restriction and inflammation after physical exercise. This ability, in turn, could mean that these individuals dont have to turn to emergency medication to address these instances.. Not only does [the supplement] reduce symptoms, which will make ...
1. JolmaA, YanJ, WhitingtonT, ToivonenJ, NittaKR, et al. (2013) DNA-binding specificities of human transcription factors. Cell 152: 327-339 doi:10.1016/j.cell.2012.12.009. 2. NobregaMA, OvcharenkoI, AfzalV, RubinEM (2003) Scanning human gene deserts for long-range enhancers. Science 302: 413 doi:10.1126/science.1088328. 3. BernsteinBE, BirneyE, DunhamI, GreenED, GunterC, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74 doi:10.1038/nature11247. 4. Pique-RegiR, DegnerJF, PaiAA, GaffneyDJ, GiladY, et al. (2011) Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data. Genome Res 21: 447-455 doi:10.1101/gr.112623.110. 5. SongL, CrawfordGE (2010) DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells. Cold Spring Harb Protoc 2010: pdb.prot5384 doi:10.1101/pdb.prot5384. 6. YanJ, EngeM, WhitingtonT, DaveK, LiuJ, et al. (2013) Transcription factor ...
The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.. Research Areas: computational biology, biomedical engineering, DNA, genomics, RNA ...
The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.. Research Areas: computational biology, biomedical engineering, DNA, genomics, RNA ...
There are a growing number of reports on the sub-physiological temperature culturing of mammalian cells for increased recombinant protein yields. However, the effect varies and the reasons for the enhancement are not fully elucidated. Expression of cold-inducible RNA-binding protein (cirp, also called cirbp or hnRNP A18) is known to be induced in response to mild, but not severe, hypothermia in mammalian cells. To clarify the molecular mechanism underlying the induction and to exploit this to improve the productivity of recombinant proteins, we tried to identify the regulatory sequence(s) in the 5′ flanking region of the mouse cirp gene. By transiently transfecting HEK293 cells with plasmids expressing chloramphenicol acetyltransferase as a reporter, we found that the cirp 5′ flanking region octanucleotide 5′-TCCCCGCC-3′ is a mild-cold responsive element (MCRE). When 3 copies of MCRE were placed upstream of the CMV promoter and used in transient transfection, reporter gene expression was
The authors identified more than 6200 candidate enhancer sequences in adult and fetal human hearts. Interestingly, comparison of putative enhancers from human fetal tissue and age-matched mouse myocardium revealed considerable species-specific differences, as only about one-fifth of fetal human heart enhancer candidates coincided with significant peaks at the orthologous site in the mouse genome. Despite the poor sequence conservation between human and mouse enhancers, the top candidates in each species shared a similar collection of transcription factor binding sites, providing a possible explanation for the activity of even poorly conserved human heart enhancers in transgenic mouse assays, which validated 43 of 65 candidate enhancers tested (66%), a significantly larger proportion than what can be expected by chance alone. Additional support that these genomic regions function as enhancers in human myocardial tissue came from statistical enrichment analysis of functional gene annotations that ...
In article ,1992Aug7.013257.12200 at, rbradbur at (Robert Bradbury) writes: , I am interested in obtaining opinions in two areas: , , 1) Are there databases which contain a list of the known promoter/enhancer , sequences for eukaryotes and/or is there software which can use this , information to identify these regions in a given sequence? I would , prefer packages which are designed for this specific task rather than , a collection of GCG commands which will always be out of date given the , ever increasing number of promoter/enhancer sequences. , , 2) Could people send me brief notes regarding their experience with PC , (DOS or UNIX) based software packages for sequence analysis (scanning , CD-ROM databases, sequence comparisons, PCR primer and probe design, etc). , Im interested in stand-alone systems which do not require large computers. , E-mail response is fine, I will post a summary for general reference. , , Thanks, , Robert Bradbury ...
translation start. Figure 1 (B) The region from -618 to +192 of the TNF gene is shown in full sequence including the polymorphisms (G/A exchanges and C-stretch). The binding sites for transcription factors (bold letters) are underlined for each factor, overlapping binding sites for two factors are underlined twice. The promoter region contains the following binding sites: kB enhancer 2/CK-1, kB enhancer 3, TNF repressor site (TRS) showing a 10bp sequence homologous to the AP-2 binding site, Y-Box, an Ets binding element in direct juxtaposition to an AP-1/ATF-like palindromic position, NFAT/k3 binding site of NFkB, SP-1 and a TATA-box. TNF-a induction is mostly regulated by the k3 binding site of NFkB. This k3 binding site also binds NFAT, resulting in a cyclosporin A sensitive TNF-a induction.. IL-1 and GM-CSF in synovial cells. However, there is a strong synergism between TNFa and IL-1 in the induction of human articular cartilage degradation during prolonged culture.. In collagen-induced ...
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Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate ...
Background Although technological advances allow increased tumor profiling now, a detailed knowledge of the mechanisms resulting in the introduction of different cancers remains elusive. after that created an analytical strategy known as Tracing Enhancer Systems using Epigenetic Attributes that correlates DNA methylation amounts at enhancers with gene manifestation to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de ...
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First, we observed that during the E2‐mediated apoptotic response in MCF7 cells, a physical association between JMJD3 and the AF1 of ERα leads to their co‐recruitment to the enhancer of the anti‐apoptotic gene BCL2, resulting in H3K27me3 demethylation and subsequent gene activation. Therefore, we propose that the repressive chromatin state caused by H3K27 methylation in ERα‐dependent cancerous cells is permissive for the regulation of BCL2 following stimulation by E2 transcription by a mechanism that comprises the interdependent recruitment of ERα and JMJD3. The knockdown of JMJD3 in this context causes apoptosis, since the cells are rendered more sensitive to apoptotic demise in the absence of expression of the anti‐apoptotic gene BCL2. It is of interest that the enhancer region of BCL2 in unstimulated MCF7 cells shows a poised enhancer signature (H3K4me1/H3K27me3) similar to what is observed in a subset of key developmental regulatory genes (Rada‐Iglesias et al, 2011). Studies ...
Blood Trait Enhancers. Blood cell traits both represent an auspicious model to investigate genetic determinants of human phenotypic diversity and are themselves of direct clinical significance. GWAS have identified numerous loci critical for hematopoiesis, but the underlying elements and genes responsible have in only a few cases been identified and validated. We hypothesize that common genetic enhancer variation is a paradigm for the determination of traits by modulating lineage-specific gene expression. E.g. we find that ~50% of the GWAS-marked loci associated with fundamental erythroid traits have at least one trait-associated variant falling directly within an erythroid enhancer, which represents highly significant enrichment as compared to control variants or enhancers. Many enhancers are thought to be redundant or compensated fine-tuners of gene regulation, for which genetic variation has minimal impact on gene expression. We hypothesize that trait-associated enhancers are critical nodes ...
The Genetics Society of America (GSA), founded in 1931, is the professional membership organization for scientific researchers and educators in the field of genetics. Our members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level.. Online ISSN: 1943-2631. ...
SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings ...
In the present study, we generated two lines of adipose tissue-specific mutant FoxO1 transgenic mice (aP2-FLAG-Δ256) using an adipose tissue-specific 5.4-kb promoter/enhancer fragment of the mouse aP2 gene. In both lines, FLAGΔ256 is expressed in BAT much more than WAT under a normal diet. The aP2-FLAG-Δ256 showed improved glucose tolerance and insulin sensitivity under a high-fat diet. Overexpression of FLAGΔ256 in WAT lead to increased visceral fat mass, increased small adipocytes, and altered expression levels of adipose tissue-related genes, such as Fasn, adiponectin, Slc2a4, Retn, Pparg, Tnf, and Ccr2. Furthermore, overexpression of FLAGΔ256 in BAT leads to increased oxygen consumption accompanied with increased expression of PGC-1α, Ucp1, and Adrb3.. Interestingly, in the present study, a high-fat diet increased the expression level of FLAGΔ256 in WAT as well as BAT. Because it has been reported that a high-fat diet induced aP2 gene expression and content (39), it can be speculated ...
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In order to support the duty of disclosure of PCE use, one must first of all clarify what properties they usually or at least frequently present, in accordance to what was found in the literature. Namely, the enhancer has acute and/or chronic effects. In the first case, shortly after taking the drug the performance is significantly better than average; in the second case, there is a growing or lasting effect, which, however, is set to diminish when one stops taking the drug; those effects are significant (there is a visible difference between taking and not taking the drug) and sometimes dramatic; a third feature, not directly related to enhancers as such, is their varying safety, availability, and legal permissibility, which might either induce people to take them or refrain them from doing so. 2 Recent reviews [57, 58] raise some doubts about the properties attributed to the PCE available today and by this fact conclude that the diffusion of enhancers should not constitute a particular ...
The AAT gene contains at least two enhancer elements , one at the 5 end of the gene and the other at the 3 end. The 5 enhancer is dominant under basal conditions and, following stimulation with IL-6 and related cytokines, both enhancers are essential and the 3 enhancer plays a major role.. Interferon γ and transforming growth factor β also modulate the hepatocyte response to IL-6. In addition to cytokines having an effect on AAT gene regulation, dexamethasone and oestrogen may have a stimulatory effect on gene regulation.. Monocyte AAT production appears to be primarily under the control of IL-6, although lipopolysaccharide , interleukin-1β (IL-1β) and tumour necrosis factor α (TNFα) all cause a 2±3-fold increase in AAT production by peripheral blood monocytes.. ...
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Mammals are characterised by a wide range of morphological diversity arising from a largely consistent set of genes. A significant fraction of these differences are assumed to derive from differences in transcriptional regulation. We have created maps of transcription factor binding, chromatin organising proteins and active enhancers and promoters across a large number of mammalian species in an attempt to understand these changes at a molecular level. These data provide insight into the evolutionary origin and persistence of regulatory sequences as well as characterise the vast majority of regulatory regions that are not shared in the common ancestor of all mammals. By investing both major mammalian orders and closely related rodent species, we can understand the greater context for the first steps of evolutionary change between species. We have also estimated the contribution of individual transcription factor binding events to tissue-specific regulation and determined the mode of inheritance for
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Nature of enhancer of SD". Genetics. 107 (3): 423-34. PMC 1202333. PMID 6428976.. ... as a lineage without the selfish genetic elements should out-compete a lineage with the selfish genetic element. Second, the ... An early striking example of hybrid dysgenesis induced by a selfish genetic element was the P element in Drosophila.[98][99] If ... The P element story is also a good example of how the rapid co-evolution between selfish genetic elements and their silencers ...
Genetic Elements within Yeast Mitochondrial and Mouse Immunoglobulin Introns (Sequence, Enhancer, Technique) (PhD thesis). ... and completed a PhD in biochemistry and molecular biology working on mobile genetic elements within introns of yeast ... His team is the first to tackle a genome-scale change in the genetic code. This was done in a 4.7 million basepair genome of an ... The future of genetic codes and BRAIN codes (Dr. Church's seminar at the NIH on 8 February 2017). ...
A genetic insulator is a boundary element that plays two distinct roles in gene expression, either as an enhancer-blocking code ... Genetic approaches may miss functional elements that do not manifest physically on the organism, evolutionary approaches have ... Many introns appear to be mobile genetic elements. Studies of group I introns from Tetrahymena protozoans indicate that some ... Cis-regulatory elements are sequences that control the transcription of a nearby gene. Many such elements are involved in the ...
cis-regulatory element Enhancer (genetics) Epistasis Genetic correlation Metabolic network Metabolic supermice Polygene Paaby, ... Sickle cell anemia is a genetic disease that causes deformed red blood cells with a rigid, crescent shape instead of the normal ... Genetic correlations and responses to selection most often exemplify pleiotropy. Pleiotropic traits had been previously ... 2007). "Genetic constraints on protein evolution". Crit. Rev. Biochem. Mol. 42 (5): 313-326. doi:10.1080/10409230701597642. PMC ...
... known to drive cancer-promoting gene expression programs through creation of distant genetic elements called super enhancers. ... There is no genetic predisposition for developing ARMS, but there are a few genetic recombination events that occurs to cause ... "PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability". Cancer Discovery. 7 (8): 884-899. ... and most cases occur sporadically with no genetic predisposition. PAX3-FOXO1 is now ...
Bellen was a leader in the development of P element-mediated enhancer detection which allows for discovery and manipulation of ... "A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases". Cell. 159 (1): 200-14. doi: ... Nagarkar-Jaiswal S, DeLuca SZ, Lee PT, Lin WW, Pan H, Zuo Z, Lv J, Spradling AC, Bellen HJ (2015). "A genetic toolkit for ... Through unbiased forward genetic screens designed to detect perturbations in neuronal function, he has uncovered many genes ...
Nature of enhancer of SD". Genetics. 107 (3): 423-34. doi:10.1093/genetics/107.3.423. PMC 1202333. PMID 6428976. Brittnacher JG ... introns as mobile genetic elements Junk DNA Mobile genetic elements Mutation Noncoding DNA Retrotransposon Transposable element ... as a lineage without the selfish genetic elements should out-compete a lineage with the selfish genetic element. Second, the ... The P element story is also a good example of how the rapid co-evolution between selfish genetic elements and their silencers ...
Katsuoka, F (2005). "Genetic evidence that small maf proteins are essential for the activation of antioxidant response element- ... Sun, J (2002). "Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene". EMBO J. 21 (19): 5216-24. doi: ... Wang, X (2010). "Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at ... It has been proposed that the latter sequences are classified as CNC-sMaf-binding elements (CsMBEs). It has also been reported ...
Another impact for science of this work was the discovery that small genetic elements upstream of the transcription start site ... Lenz, J; Celander D; Crowther RL; Patarca R; Perkins DW; Sheldon A; Haseltine WA (1984). "Enhancer Sequences that Determine ... Cohen; Terwilliger E; Haseltine WA (1991). Haseltine WA, Wong-Staal F (ed.). Genetic Structure and Regulation of HIV-1 (EA ed ... 1991). Haseltine WA, Wong-Staal F (ed.). Genetic Structure and Regulation of HIV-1. Raven Press. pp. 457-471. Haseltine, WA; ...
Moreover, many regulatory elements function only in certain cell types and specific conditions. Enhancer detection in ... characterized the effects of human genetic variation on non-coding regulatory element function, measuring the activity of 100 ... Wilson, C; Pearson RK; Bellen HJ; O'Kane CJ; Grossniklaus U; Gehring WJ (September 1989). "P-element mediated enhancer ... 4.5% of enhancers were located at transcription start sites (TSS), suggesting that these enhancers can start transcription and ...
Enhancer+Elements,Genetic at the US National Library of Medicine Medical Subject Headings (MeSH) TFSEARCH JASPAR ENCODE threads ... These include enhancers, silencers, insulators and tethering elements. Among this constellation of elements, enhancers and ... Enhancers are regions of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene ... Secondary enhancers, or "shadow enhancers", may be found many kilobases away from the primary enhancer ("primary" usually ...
Insertion between promoter and upstream enhancers => loss of enhancer function/hijack of enhancer function for reporter gene.† ... To use this process as a useful and controllable genetic tool, the two parts of the P element must be separated to prevent ... began their experiment by constructing a genetic sequence consisting of the Hmox-1 transposable element and transposase from ... The hijack of an enhancer from another gene allows the analysis of the function of that enhancer. This, especially if the ...
... "enhancers" drives the polka-dot pattern on the wings of D. guttifera. These enhancers were a subset of cis-regulatory elements ... This selfish X chromosome is one of a number of selfish genetic elements in the Quinaria and Testacea Drosophila species groups ... the impact of various genetic elements in natural populations, and speciation. Various Quinaria group species have contributed ... Lactate-producing bacteria are a core element of the human gut microbiome, and abundance of lactate is implicated in colonic ...
Enhancer-like structures in middle repetitive DNA elements of eukaryotic genomes. Genetics (USSR/Russia), 22, 357-367 "AMEA-nın ... The existence of the sites homological to the regulatory site of heat-shock in mobile genetic elements. Genetics (USSR/Russia ... Some structural elements in DNA sequence from Balbiani ring of IV Chromosome of Chironomus thummi. Proceedings of Academy of ... Department of Molecular-Genetic Bases of Production Processes, Institute of Botany, ANAS (1987-1989). structure and evolution ...
Lamb MJ, Jablonka E (2005). Evolution in four dimensions: genetic, epigenetic, behavioral, and symbolic variation in the ... Slotkin RK, Martienssen R (April 2007). "Transposable elements and the epigenetic regulation of the genome". Nature Reviews ... This enzyme utilizes a catalytically active site called the SET domain (Suppressor of variegation, Enhancer of zeste, Trithorax ... These are normal genetic diseases caused by gene deletions or inactivation of the genes, but are unusually common because ...
... which is responsible for suppressing an upstream enhancer element known as hs1473. When H2AFY is removed, the enhancer is ... Liebenberg Syndrome is a result of one of two different genetic mutations. The first is a deletion upstream of the PITX1 gene ... Liebenberg syndrome is a rare autosomal genetic disease that involves a deletion mutation upstream of the PITX1 gene, which is ... This move introduces two enhancers from chromosome 18 to move to a position directly upstream of PITX1 on chromosome 5. The ...
In particular the goal is to link genetic and epigenomic modifications with the enhancers and promoters which they interact ... Such elements are characterized by the massive presence of insulator binding proteins CTCF. Secondly, boundary regions block ... Only rare genetic variants show the stochastic type of gene regulation. The study made by Onuchic et al. was aimed to construct ... CoRSIVs are under-represented in the proximity of genes, in heterochromatic regions, active promoters, and enhancers. They are ...
Some cases of polydactyly are caused by mutations in the ZRS, a genetic enhancer that regulates expression of the Sonic ... ZRS is a noncoding element, 800 kilobasepairs (kb) remote to the target gene SHH. An ectopic expression of SHH is seen on the ... Genetic work studying the DNA basis of the condition indicates that many different mutations in the same ZRS area can all lead ... In the case of preaxial polydactyly of the Maine Coon cat (Hemingway mutant) a mutation of the cis-regulatory element ZRS (ZPA ...
The non-coding region of genome contain many important regulatory elements including promoter, enhancer and insulator, any kind ... Genetic variants that located in distal regulatory region can affect the binding motif of TFs, chromatin regulators and other ... SNPs are the most common genetic variant found in all individual with one SNP every 100-300 bp in some species. Since there is ... Li MJ, Yan B, Sham PC, Wang J (May 2015). "Exploring the function of genetic variants in the non-coding genomic regions: ...
Transposable elements are regions of DNA that can be inserted into the genetic code through one of two mechanisms. These ... A mutation in a promoter region, enhancer region or transcription factor binding region can also result in either a loss of ... These grounded prophages and other such genetic elements are sites where genes could be acquired through horizontal gene ... The genetic code is made up of sequences of four nucleotide bases: Adenine, Guanine, Cytosine and Thymine, commonly referred to ...
... relying on genetic switches called enhancers that drive the polka-dot pattern on the wings of D. guttifera. These enhancers are ... cis-regulatory elements, which can promote new wing patterns by modifying gene expression, rather than the actual protein being ...
Promoter/enhancer connections: distal cis-regulatory elements, such as enhancers are in charge of modulating the activity of ... data gives an idea of the great complexity regulating the genetic expression in the human genome and the quantity of elements ... These regions have been shown to map many types of cis-regulatory elements including promoters, enhancers, insulators, ... ENCODE Project: Regulatory Elements DB Plant DHSs : PlantDHS Wang, YM; Zhou, P; Wang, LY; Li, ZH; Zhang, YN; Zhang, YX (2012 ...
These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins ... As in DNA, genetic information in mRNA is contained in the sequence of nucleotides, which are arranged into codons consisting ... portions of coding regions may serve as regulatory sequences in the pre-mRNA as exonic splicing enhancers or exonic splicing ... Genetic variants in 3' UTR have also been implicated in disease susceptibility because of the change in RNA structure and ...
An enhancer trap is a method in molecular biology. The enhancer trap construct contains a transposable element and a reporter ... On top of this, the construct usually includes a genetic marker, e.g., the white gene producing red-colored eyes in Drosophila ... Gene trapping P element Andrea Brand and Norbert Perrimon (1993). Targeted gene expression as a means of altering cell fates ... The most common and basic enhancer traps are: P[lacZ] from the bacterium E. coli and P[GAL4] from yeast. There exists a large ...
Einvik, C; Elde, M; Johansen, S (17 September 1998). "Group I twintrons: genetic elements in myxomycete and schizopyrenid ... Scamborova P, Wong A, Steitz JA (March 2004). "An intronic enhancer regulates splicing of the twintron of Drosophila ... The majority of these twintrons have been characterized within the Euglena chloroplast genome but these elements have also been ... the internal and external introns comprising the twintron element are from the same category; group I internal to group I, ...
Enhancers are sites on the DNA helix that are bound by activators in order to loop the DNA bringing a specific promoter to the ... Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (Ac) and Dissociator (Ds ... The 3'-UTR often contains miRNA response elements (MREs). MREs are sequences to which miRNAs bind. These are prevalent motifs ... Enhancers are much more common in eukaryotes than prokaryotes, where only a few examples exist (to date).[3] Silencers are ...
2008). Molecular genetic pathology. Totowa, NJ: Humana. p. 96. ISBN 978-1-59745-405-6. . Retrieved 31 December 2016.. ... Key elements. *Ribosome. *Transfer RNA (tRNA). *Ribosome-nascent chain complex (RNC). *Post-translational modification ... Genetics attempts to predict how mutations, individual genes and genetic interactions can affect the expression of a phenotype ... Molecular biology arose as an attempt to answer the questions regarding the mechanisms of genetic inheritance and the structure ...
An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element". Science. 346 (6215): 1373-7. ... This technology has further aided the genetic and epigenetic study of chromosomes both in model organisms and in humans.[not ... Adenocarcinoma of the lung can be caused by a duplication of enhancer element for MYC gene. T-cell acute lymphoblastic leukemia ... Beta thalassemia is a certain type of blood disorders caused by a deletion of LCR enhancer element. Holoprosencephaly is ...
Similarities with enhancers[edit]. See also: Enhancers. Another regulatory element located upstream of the gene is an enhancer ... "Control of Genetic Systems in Prokaryotes and Eukaryotes". University of Illinois at Chicago. Retrieved 2 April 2013.. ... DNA looping is also a model function used by enhancers in order to shorten the proximity of the promoter to the enhancer. ... which are the classical silencer element and the non-classical negative regulatory element (NRE). In classical silencers, the ...
NEMO deficiency syndrome is a rare genetic condition relating to a fault in IKBKG that in turn activates NF-κB. It mostly ... NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA ... Certainly, learning and memory could be influenced by transcriptional changes in astrocytes and other glial elements. And it ... Indeed, this confounds the interpretation of p105-knockout studies, where the genetic manipulation is removing an IκB (full- ...
cis-regulatory element. *Enhancer (genetics). *Epistasis. *Genetic correlation. *Metabolic network. *Metabolic supermice ... Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is genes that ... Sickle cell anemia is a genetic disease that causes deformed red blood cells with a rigid, crescent shape instead of the normal ... This article is about genetic pleiotropy. For drug pleiotropy, see Pleiotropy (drugs). ...
Enhancers are long-range regulatory elements that increase promoter activity while silencers repress promoter activity. ... Genetic engineering[edit]. TATA box modification[edit]. Evolutionary changes have pushed plants to adapt to the changing ... the downstream promoter element (DPE) in cooperation with the initiator element (Inr) bind to the transcription factor II D ( ... The TATA box is considered a non-coding DNA sequence (also known as a cis-regulatory element). It was termed the "TATA box" as ...
sequence-specific enhancer binding RNA polymerase II transcription factor activity. · transcription factor binding. · zinc ion ... Gene information at Genetic Home Reference. *Language and Genetics Research at the Max Planck Institute for Psycholinguistics ... Apetala 2 · EREBP(英语:Ethylene-responsive element binding protein) · B3. (0.6) Miscellaneous ...
Maston, G. A.; Evans, S. K.; Green, M. R. (2006). "Transcriptional Regulatory Elements in the Human Genome". Annual Review of ... Jacob F; Monod J (June 1961). "Genetic regulatory mechanisms in the synthesis of proteins". J Mol Biol. 3 (3): 318-56. doi: ... Pennacchio, L. A.; Bickmore, W.; Dean, A.; Nobrega, M. A.; Bejerano, G. (2013). "Enhancers: Five essential questions". Nature ... Andrews, Christine A. (2010). "Natural Selection, Genetic Drift, and Gene Flow Do Not Act in Isolation in Natural Populations ...
Quantitative genetics focuses on genetic variance due to genetic interactions. Any two locus interactions at a particular gene ... It may be caused by several mechanisms, for example transvection, where an enhancer from one allele acts in trans to activate ... Charlesworth B, Charlesworth D (2010). Elements of Evolutionary Genetics. Roberts and Company Publishers.. ... In this regression, the observed two locus genetic effects are treated as dependent variables and the "pure" genetic effects ...
The RNA carries genetic information to code for the production of new infectious particles. More recently virus research has ... However some plant viruses do not use cap, yet translate efficiently due to cap-independent translation enhancers present in 5 ... Hull, Robert (November 2001). "Classifying reverse transcribing elements: a proposal and a challenge to the ICTV". Archives of ... Genetic and Structural Analyses of Pea Embryo Invasion by Pea Seed-Borne Mosaic Virus". The Plant Cell. 6: 777-787. doi:10.2307 ...
Single-cell resolution can uncover the roles of genetic mosaicism or intra-tumor genetic heterogeneity in cancer development or ... To target larger non-poly(A) RNAs, such as long non-coding mRNA, histone mRNA, circular RNA, and enhancer RNA, size selection ... is widespread along the genome and plays an important role in regulating gene expression by repressing transposable elements.[ ... Single-nucleotide polymorphisms (SNPs), which are a big part of genetic variation in the human genome, and copy number ...
AU-rich element decayEdit. The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts ... Messenger RNA (mRNA) is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they ... portions of coding regions may serve as regulatory sequences in the pre-mRNA as exonic splicing enhancers or exonic splicing ... These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins ...
RNA polymerase II distal enhancer sequence-specific DNA binding. • sequence-specific DNA binding. • DNA binding. • ... 1osh: A Chemical, Genetic, and Structural Analysis of the nuclear bile acid receptor FXR ... and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes.[6] ... transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding. • chenodeoxycholic acid binding. • ...
Presence of repeated elements at its border and absence of promoter-associated sequences". Journal of Molecular Biology. 167 (1 ... This new exon contains the ORF for a reporter gene that can now be expressed using the enhancers that control the target gene. ... "Exon Trapping: a Genetic Screen to Identify Candidate Transcribed Sequences in Cloned Mammalian Genomic DNA". Proceedings of ... Morpholino oligos can also be targeted to prevent molecules that regulate splicing (e.g. splice enhancers, splice suppressors) ...
Mercury (element) Thallium Lead Bismuth Polonium Astatine Radon Francium Radium Actinium Thorium Protactinium Uranium Neptunium ... Ahmed AR, Jha AN, Davies SJ (2012). "The efficacy of chromium as a growth enhancer for mirror carp (Cyprinus carpio L): an ... through dietary supplements poses no genetic-toxic risk.[133] In the US, the Occupational Safety and Health Administration ( ... Chromium is a chemical element with the symbol Cr and atomic number 24. It is the first element in group 6. It is a steely-grey ...
Though genetic defects causing iron deficiency have been studied in rodents, there are no known genetic disorders of human iron ... Wintergerst, E. S.; Maggini, S.; Hornig, D. H. (2007). "Contribution of Selected Vitamins and Trace Elements to Immune Function ... "Enhancers and inhibitors of iron absorption". Advanced Nutrition and Human Metabolism (5th ed.). Belmont, California: ...
... myocyte enhancer factor 2 (MEF2) and 14-3-3.[5][6] All three HDACs work to repress the myogenic transcription factor MEF2 which ... Histone modification is now considered a major regulatory mechanism that is involved in many different stages of genetic ... Key elements. *Ribosome. *Transfer RNA (tRNA). *Ribosome-nascent chain complex (RNC). *Post-translational modification ...
... or highly conserved elements within the mammalian genome that are both transcribed and fulfil enhancer functions suggest Evf-2 ... For example, the induction of an antisense transcript by a genetic mutation led to DNA methylation and silencing of sense genes ... Alu elements in humans and analogous B1 and B2 elements in mice have succeeded in becoming the most abundant mobile elements ... The abundance and distribution of Alu elements and similar repetitive elements throughout the mammalian genome may be partly ...
Promoters represent critical elements that can work in concert with other regulatory regions (enhancers, silencers, boundary ... Some cases of many genetic diseases are associated with variations in promoters or transcription factors. ... Some promoters contain one or more upstream promoter element (UP element) subsites[5] (consensus sequence 5'-AAAAAARNR-3' when ... and a B recognition element (BRE), which is recognized by the general transcription factor TFIIB.[4][7][8] The TATA element and ...
Genetic engineering. Further information: Molecular biology, Nucleic acid methods, and Genetic engineering ... The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom ... Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which ... known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence ...
... "elements" (enhancers and silencers) on the pre-mRNA transcript itself. These proteins and their respective binding elements ... in addition to their contribution to genetic disease susceptibility. Indeed, genome-wide studies in humans have identified a ... For example, a splicing factor that serves as a splicing activator when bound to an intronic enhancer element may serve as a ... In addition to the position-dependent effects of enhancer and silencer elements, the location of the branchpoint (i.e., ...
lncRNAs used had lengths between ~90-4800 nt, and included the NoRC-binding pRNA, three enhancer-transcribed RNAs (eRNAs) FALEC ... to distinguish lncRNA function from other confounding factors like cryptically encoded peptides or functional DNA elements. ... Genetic engineering. *LncRNA. *Synthetic biology. Hidden categories: *Articles needing additional references from March 2017 ...
This can activate the CREB transcription factor (cAMP Response Element-Binding) that will bind to the CRE (cAMP Responsive ... These two transcription factors influence the activity of NUE (NIS Upstream Enhancer), which is essential for initiating ... This genetic technique is called gene targeting. Once NIS is transferred in these cells, the patient is treated with ... "The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and ...
"Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence". Nat. Genet. 41 (3): 359-64 ... "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167-78. PMC 3086810. PMID ... SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer." ... "Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia.". Proc. Natl. Acad. Sci. U.S.A. 95 ( ...
"Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences". ... to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements ... "Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus ...
Shakhmuradov IA, Kolchanov NA, Solovyev VV, Ratner VA (1986) Enhancer-like structures in middle repetitive DNA elements of ... The existence of the sites homological to the regulatory site of heat-shock in mobile genetic elements. Genetics (USSR/Russia ... In: "Computer analysis of genetic macromolecules . Structure, Function and Evolution", World Scientific, 1993, 181-186 ... In: "Computer analysis of genetic macromolecules . Structure, Function and Evolution", World Scientific, 1993, 186-192 ...
St Johnston D (2002). "The art and design of genetic screens: Drosophila melanogaster". Nat Rev Genet. 3 (3): 176-188. doi: ... 2007). "Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome". Nat Genet ... Lawson N. D., Wolfe S. A. (2011). "Forward and Reverse Genetic Approaches for the Analysis of Vertebrate Development in the ...
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that presents with variable clinical abnormalities including ... It has been proposed that cohesin promotes the interaction between enhancers and promoters for regulating gene transcription ... contributes to facilitating inter-chromatid contacts mediating distant-element interactions and to creating chromosome domains ...
Promoters represent critical elements that can work in concert with other regulatory regions (enhancers, silencers, boundary ... Some cases of many genetic diseases are associated with variations in promoters or transcription factors. ... Many other elements/motifs may be present. There is no such thing as a set of "universal elements" found in every core promoter ... Some promoters contain one or more upstream promoter element (UP element) subsites[7] (consensus sequence 5'-AAAAAARNR-3' when ...
Evolution of genetic systems. *Evolvability. *Mutational robustness. *Neutral networks. *Evolution of sexual reproduction ...
These results suggest that NOBOX gene is a strong autosomal candidate for POF and its genetic mechanism involves ... the NOBOX DNA binding elements (NBEs). There are three NBEs that have been identified: 5'-TAATTG-3', 5'-TAGTTG-3', and 5'- ... "Clinical, biological and genetic analysis of prepubertal isolated ovarian cyst in 11 girls". PLOS One. 5 (6): e11282. doi ... homeodomain is important to researchers and clinicians to develop diagnostic and therapeutic approaches for POF such as genetic ...
Genetic diversity of plague in First Pandemic. A study explores the genetic diversity of plague bacteria in the First Pandemic. ... Enhancer elements and enhancer-binding proteins are widespread components of transcriptional regulation systems in eukaryotes ( ... An enhancer element located downstream of the major glutamate dehydrogenase gene of Bacillus subtilis. Boris R. Belitsky and ... Another unusual feature of the rocG enhancer element is that it is shared by the rocG gene and the downstream rocABC operon. We ...
Enhancer Elements, Genetic* * Epigenesis, Genetic * Gene Expression Profiling * Gene Expression Regulation* * Histones / ... Our results indicate that this signature is that of super-enhancers, a category of broad enhancers regulating genes defining ... Together, our results provide evidence for preferential down-regulation of genes controlled by super-enhancers in HD striatum ... Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntingtons disease ...
... but was unable by itself to stimulate transcription from a remote enhancer position. Here we … ... Enhancer Elements, Genetic* * HeLa Cells * Humans * Molecular Sequence Data * Plasmids * Promoter Regions, Genetic* ... Different activation domains stimulate transcription from remote (enhancer) and proximal (promoter) positions EMBO J. 1992 ... usually in response to a remote enhancer. General activation domains, derived from VP16, GAL4, p65 (NF-chi B), TFE3, ITF-1 ...
Rubin GM, Spradling AC (1982) Genetic transformation ofDrosophila with transposable element vectors. Science 218:348-353PubMed ... In: Shapiro JA (ed) Mobile genetic elements. Academic Press, New York, pp 329-361Google Scholar ... of thetom element contain such an eye imaginal disc-specific enhancer, usingD. melanogaster transformants containing alacZ gene ... Karess RE, Rubin GM (1984) Analysis of P transposable element functions inDrosophila. Cell 38:135-146PubMedGoogle Scholar ...
Enhancer Elements, Genetic*. Escherichia coli / genetics. Globins / genetics. Herpesvirus 4, Human / genetics*. Humans. ... ZRE-B plus the R-responsive element) positioned as an enhancer. ZRE-B is therefore not part of the R-inducible enhancer. We ... 64:313-321, 1990). We show here that domain B is an R-responsive element in HeLa cells and is therefore not an EB1-responsive B ... specific element. However, there is an EB1-binding site (ZRE-B) located within the R-responsive enhancer region. ZRE-B can be ...
... which they use to identify somatic copy-number alterations affecting cis-regulatory elements in cancer. They find that enhancer ... We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal ... enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). ... yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains ...
1A), was tested in the enhancer-blocking assay using the enhancers of the yellow and white genes. The eye enhancer was inserted ... Genetic transformation of Drosophila with transposable element vectors. Science 218 : 348-353. ... The Fab-7 element of the bithorax complex attenuates enhancer-promoter interactions in the Drosophila embryo. Genes Dev. 10 : ... This element (the M340 insulator) effectively blocks the enhancers of the yellow and white genes expressing at the pupa stage. ...
An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74. doi:10.1038/nature11247. ... An ankylosing spondylitis-associated genetic variant in the IL23R-IL12RB2 intergenic region modulates enhancer activity and is ... An ankylosing spondylitis-associated genetic variant in the IL23R-IL12RB2 intergenic region modulates enhancer activity and is ... TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 2012;488:508-11. doi:10.1038/ ...
Nature of enhancer of SD". Genetics. 107 (3): 423-34. doi:10.1093/genetics/107.3.423. PMC 1202333. PMID 6428976. Brittnacher JG ... introns as mobile genetic elements Junk DNA Mobile genetic elements Mutation Noncoding DNA Retrotransposon Transposable element ... as a lineage without the selfish genetic elements should out-compete a lineage with the selfish genetic element. Second, the ... The P element story is also a good example of how the rapid co-evolution between selfish genetic elements and their silencers ...
Nature of enhancer of SD". Genetics. 107 (3): 423-34. PMC 1202333. PMID 6428976.. ... as a lineage without the selfish genetic elements should out-compete a lineage with the selfish genetic element. Second, the ... An early striking example of hybrid dysgenesis induced by a selfish genetic element was the P element in Drosophila.[98][99] If ... The P element story is also a good example of how the rapid co-evolution between selfish genetic elements and their silencers ...
TBX transcription factors; arrhythmias; cardiac conduction system; enhancers; epigenetic variation; genetic variation ... Gene regulatory elements of the cardiac conduction system.. van Duijvenboden K1, Ruijter JM, Christoffels VM. ... The role of variation in gene regulatory elements in the cardiac conduction system has recently been demonstrated by studies on ... Furthermore, the risk variant of the allele abrogated enhancer function in both cases. Functional studies on regulatory DNA ...
8I); moreover, it showed the same genetic properties as the lab550 enhancer: the expression driven by this minimal enhancer was ... We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element ( ... is able to resume the properties of the lab550 enhancer. Therefore, the lab550 enhancer is composed of several elements, or ... signal-responsive element is the visceral mesoderm specific enhancer of the dpp gene, dpp674. This enhancer is directly ...
Animals; Mice; CpG Islands; *Enhancer Elements, Genetic; *Promoter Regions, Genetic; *Transcription Initiation Site; DNA/* ... We show that Pol II and GTFs are recruited to known T cell-specific enhancers. We extend this observation to many new putative ... Finally, we also report differential recruitment of TFIID and other GTFs at promoters and enhancers. Overall, we propose that ... Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Koch, F.; Fenouil, R.; Gut, ...
Enhancer Elements, Genetic. *Flavonoids/pharmacology. *Gene Expression Regulation, Neoplastic*. *Humans. *Intracellular ... D) Box plots of the normalized counts of H3K27ac and H3K4me1 signal at YAP+ enhancer peaks or YAP− enhancers. *** p,0.0001. E) ... F) Histogram indicating the fraction of YAP− or YAP+ enhancers catalogued as regular o super- enhancers in HuCCT1 cells. G) ... YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers.. Galli GG1, Carrara M2, Yuan WC1, Valdes ...
In Science this week: a novel RNA structural element that acts as a splicing enhancer, and more. ... A genetic genealogy approach has identified "Christy Crystal Creek," the New York Times reports. ... Population Genetics Launches Competition for Genetic Association Sequencing Studies Oct 16, 2012 , Monica Heger ... Science Papers Report on Splicing Enhancer, Point of Care Test for Sexual Transmitted Disease ...
14) by genetic (15) and molecular tests (16). Besides maize, CACTA elements have been characterized from snapdragon (Tam1; ref ... It was identified originally as Enhancer (En; ref. 13) and was shown later to be homologous to the Suppressor-Mutator system ( ... Of several members of this family, the En/Spm element of maize has been best understood at the genetic and molecular levels. ... Transposable elements as causative agents of variegation and genetic variation were first discovered in maize by Barbara ...
Enhancer Elements, Genetic/*physiology; Gene Regulatory Networks; Macrophages/*cytology; MafB Transcription Factor/metabolism; ... Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Soucie, E. L.; Weng, Z.; ... Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. ... Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire ...
... including novel enhancer elements to drive "magical" type expression of genes (figure⇓). Such magical enhancers would join a ... Left) Magical enhancer element within a site of accessible chromatin in human with ancestors all possessing magical abilities ( ... This is not a simple single gene effect and may be related to "magical enhancer" elements ... Risch N. The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic ...
Článek Genetic Landscape of Open Chromatin in Yeast Článek Deleterious Alleles in the Human Genome Are on Average Younger Than ... mark distal enhancers [34]-[37]. Using this set of histone marks, we previously identified thousands of enhancer elements in ... we defined a large group of enhancer elements co-bound by SOX2 and BRN2 in NPCs. We identified known functional enhancers bound ... SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State Download PDF České ...
Schmitt C. A., Rosenthal C. T., Lowe S. W. Genetic analysis of chemoresistance in primary murine lymphomas. Nat. Med., 6: 1029- ... The NF-κB and Sp1 elements are conserved in the human IgH enhancers as well as in the murine IgH enhancers, suggesting that ... Critical Elements of the Immunoglobulin Heavy Chain Gene Enhancers for Deregulated Expression of Bcl-2. Caroline A. Heckman, ... Enhancer HS4 was the most active one with the bcl-2 promoter. To locate the elements that contributed to this activity, we ...
Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. Erythroid cells with a ... and genome-editing approaches in characterizing noncoding regulatory elements in phenotype-relevant cells. Our study supports ... enhancer alleles deleted. None of these clones has an inversion allele. One clone was identified with 1 deletion allele and 1 ... expression in HUDEP-2 cells with 98-bp core enhancer deletion. Control (. n. = 2) refers to 1 nontargeting control clone and ...
2012 Positive selection of co-opted mobile genetic elements in a mammalian gene: if you cant beat them, join them. Mob. Genet ... many elements display enhancer activity, indicating that the lack of mammal-fish identity of these orthologous enhancers was ... 2012 The chromatin fingerprint of gene enhancer elements. J. Biol. Chem. 287, 30 888-30 896. (doi:10.1074/jbc.R111.296491). ... The fact that nPEs are mammalian novelties indicates that their cis-elements had to be created de novo before the new enhancers ...
Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells. ... An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element ... An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element ... In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers ...
Identification of enhancer elements at .... PLATFORM. Session #64. Measuring Effects of Genetic Variants with High-Throughput ... Lower frequency of genetic mosaicism .... POSTER. Statistical Genetics and Genetic Epidemiology. 2988F. Friday, Oct. 20. ... Pharmacological insights from genetic .... POSTER. Statistical Genetics and Genetic Epidemiology. 2937F. Friday, Oct. 20. ... Examining the genetic architecture of the .... PLATFORM. Session #34. Genetic Architecture of Neurological Traits. 146. ...
Immune Enhancers. The immune system is the bodys ultimate defense against infectious agents such as bacteria and viruses. It ... A healthy immune system contains elements that are in balance with one another. In a compromised immune system, the components ... also protects against genetic mistakes made in cellular replication that result in tumor or cancer growth. The immune system is ...
Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs ... SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying ... These enhancers provide a hitherto missing link by which SRY activates SOX9 in humans, and establish SOX9 enhancer mutations as ... All three enhancers showed synergistic activity and together drive SOX9 in the testis. This is the first study to identify SOX9 ...
... cell line TT is modulated by a neuroendocrine-specific enhancer fragment (nucleotides -965 to -905) containing two CANNTG ... Enhancer Elements, Genetic*. Gene Expression Regulation, Neoplastic*. Hela Cells. Humans. Molecular Sequence Data. ... In CT-negative MTC cells (RO-D81), the Ets response element was active but the two copies of E2 were not. Similar results were ... Previous Document: Identification of positive and negative regulatory elements involved in the retinoic acid/cAMP induc.... ...
Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element. Genetics 154, 237-246. ... EY and TOY are involved in so10 enhancer expression. Recent genetic analysis demonstrated that the induction of so mediated by ... lacZ staining (arrow) shows that toy is able to activate this enhancer element in the absence of endogenous ey. ... The so7TOYmt enhancer (Fig. 6D) shows a similar expression pattern as the so10TOYmt enhancer (Fig. 4G) in the posterior part of ...
... is under the control of a series of enhancer elements, one for each stripe. Each enhancer element contains binding sites for ... The BX-C mutations picked up by Lewis in his genetic screen (bx, pbx, bxd, iab2 etc) turn out to be regulatory mutations of ... In this region there are three enhancer elements that control eve expression in stripes 2, 3 and 7. Other elements, not shown ... Transcription of Ubx, abd-A and Abd-B is controlled by a series of enhancer elements, each of which is specific for a ...
1989) Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding ... Interaction between CCAAT/Enhancer Binding Protein and Cyclic AMP Response Element Binding Protein 1 Regulates Human ... Interaction between CCAAT/Enhancer Binding Protein and Cyclic AMP Response Element Binding Protein 1 Regulates Human ... Interaction between CCAAT/Enhancer Binding Protein and Cyclic AMP Response Element Binding Protein 1 Regulates Human ...
  • Integrating RNA-sequencing (RNA-seq) and chromatin-immunoprecipitation followed by massively parallel sequencing (ChIP-seq), we show that down-regulated genes in HD mouse striatum associate with selective decrease in H3K27ac, a mark of active enhancers, and RNA Polymerase II (RNAPII). (
  • Our results indicate that this signature is that of super-enhancers, a category of broad enhancers regulating genes defining tissue identity and function. (
  • Specifically, we reveal that striatal super-enhancers display extensive H3K27 acetylation within gene bodies, drive transcription characterized by low levels of paused RNAPII, regulate neuronal function genes and are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. (
  • Together, our results provide evidence for preferential down-regulation of genes controlled by super-enhancers in HD striatum and indicate that enhancer topography is a major parameter determining the propensity of a gene to be deregulated in a neurodegenerative disease. (
  • Molecular and genetic analyses have revealed that eye morphology defects of Om mutants are caused by the ectopic or excessive expression of Om genes in the eye imaginal discs of third instar larvae. (
  • It is therefore assumed that the tom element carries tissue-specific gene regulatory sequences which enhance expression of the Om genes. (
  • On the basis of these findings, it is hypothesized that ectopic and excessive expression of the Om genes in the eye imaginal discs is induced by an eye imaginal disc-specific enhancer present in the tom LTR, the effect of which may be subject to chromosomal position effects. (
  • Selfish genetic elements (historically also referred to as selfish genes , ultra-selfish genes , selfish DNA , parasitic DNA and genomic outlaws ) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no positive or a net negative effect on organismal fitness. (
  • Three well characterized maize transposons- Ac/Ds , En/Spm , and Mu ( 4 - 6 )-have been used in gene-tagging approaches to isolate a large number of plant genes ( 3 , 7 ). (
  • Thus, the identification of an active transposable element for gene tagging in sorghum could provide a new route to the isolation of the corresponding maize genes. (
  • Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis -regulatory elements (CREs) remains unclear. (
  • We have identified an insulator in the 755-bp Mcp fragment that is linked to the previously characterized Polycomb response element (PRE) and silences the adjacent genes. (
  • This insulator blocks the enhancers of the yellow and white genes and protects them from PRE-mediated repression. (
  • Church returned to graduate work at Harvard University in 1977 under Walter Gilbert , [16] and completed a Ph.D. in biochemistry and molecular biology working on mobile genetic elements within introns of yeast mitochondrial and mouse Immunoglobulin genes (1984). (
  • For example, noncoding DNA contains sequences that act as regulatory elements, determining when and where genes are turned on and off. (
  • Such elements provide sites for specialized proteins (called transcription factors) to attach (bind) and either activate or repress the process by which the information from genes is turned into proteins (transcription). (
  • E) Boxplot indicating expression levels of genes associated to YAP+ or YAP− enhancers following RNAseq in HUCCT1 cells. (
  • H) Log2 changes in gene expression between siControl / siYT treated cells for genes associated with different genomic elements 48h post transfection. (
  • This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. (
  • 3,4 Not only are important genes contained in these sequences, but also many different regulatory elements that function as key genetic switches. (
  • 3 - DNA elements that modulates how genes are transcribed into RNA and how the genome is organized. (
  • Magical enhancers regulating gene expressionmay be involved, combined with mutations at specific genes implicated in speech and hair colour such as FOXP2 and MCR1. (
  • Genetic factors that underlie traits such as height 1 and weight 2 are currently under scrutiny using genome wide association methods, yet the detection of genes predisposing to magic has been given relatively short shrift. (
  • Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. (
  • Transcriptional enhancers are cis -acting DNA elements that work as arrays of transcription factor binding sites (TFBSs) and control the transcriptional activity of genes located nearby. (
  • Finally, enhancers act at a distance and can even be embedded within neighbouring loci [ 5 - 9 ], indicating a large degree of positional freedom of enhancers in relation to the genes they control. (
  • Thus, while new protein coding genes mostly appear by duplication of pre-existing genes [ 10 ], DNA sequences within an enhancer can change quickly over evolutionary time and new enhancers can appear in new locations and replace ancient ones. (
  • Analysis of the expression patterns of these genes combined with genetic approaches , have revealed a sequential and hierarchical cascade during compound eye development. (
  • Then, in 2012, researchers proposed that eukaryotic chromosomes fold into relatively predictable structures called "topologically associating domains" (TADs), and that these structures prevent enhancers from activating genes all over the genome by effectively restricting their actions to within a few hundred thousand bases. (
  • Thus the particular constellation of maternal effect genes, gap genes and other pair-rule genes that is expressed in a given parasegment determines whether or not one of the enhancer elements is fully occupied and consequently whether eve gene transcription is activated or not in that parasegment. (
  • The promoter elements of many monocyte-specific genes contain C/EBP binding sites, including macrophage inflammatory protein 1 alpha, tumor necrosis factor alpha ( 32 ), IL-6 ( 6 , 27 , 38 ), and IL-8 ( 27 , 36 ). (
  • b) The recruitment of genes and enhancers to a repressive chromatin hub (RCH) results in their downregulation (165). (
  • It was already shown that there are many genetic interactions between different Grhl genes. (
  • In the maintenance of adult skin barrier, genetic redundancy involves the Grhl1 and Grhl3 genes, which was recently demonstrated using mouse models. (
  • Although these regulatory elements are often distant from their target genes, they affect gene expression by recruiting transcription factors to specific promoter regions. (
  • Finally, we uncovered that these elements are generally found within 1 Mb of their targets, and often regulate multiple genes. (
  • This 3-D genomic architecture allows to direct enhancer action from one gene to another, to coordinate expression of several genes or genetic loci simultaneously, to couple and control genes within one unit or several processes with the same factors, if necessary, sometimes delineating eukaryotic equivalents of prokaryotic operons. (
  • A genetic screen for mutations that dominantly suppress or enhance dRet MEN2 phenotypes identified new genes that are required for the phenotypic outcomes of dRet MEN2 activity. (
  • VIGEs integrated in such genetic programs will change expression patterns of genes that will result in different cellular behaviour and morphology. (
  • Most of the short DNA elements cluster near genes that play a decisive role during an organism's first weeks after conception. (
  • CBF is a heterodimeric complex that binds to core enhancer elements in viral and cellular genes. (
  • An enhancer is a short region of DNA that can be bound with proteins (namely, the trans-acting factors, much like a set of transcription factors ) to enhance transcription levels of genes (hence the name) in a gene cluster. (
  • AD risk variants predominantly occur in enhancers of myeloid genes. (
  • Altogether, enhancer data nominated 16 causal genes, nine of them new to AD. (
  • What genes did these enhancers control? (
  • The ability of transposable elements to epigenetically influence adjacent genes impacts genome evolution by driving substantial variation in transposon numbers between species. (
  • After working in Germany for two years on immunoglobulin class-switched antibody pairs, Neuberger returned to the LMB where he began to study the genetic elements that regulated immunoglobulin gene expression in cells and mice transfected with genomic fragments containing functional immunoglobulin genes. (
  • Neuberger's identification of the controlling elements for immunoglobulin genes proved to be an important component in the development of a biotechnology that remains a major focus of the pharmaceutical industry. (
  • One proposed mechanism of action of the SNPs is that they would affect the activity of enhancer elements regulating critical target genes. (
  • Another key element concerns the involvement of several identified candidate genes in the immune response to viruses, thus highlighting the importance of viral infections in the risk of asthma. (
  • Using a combination of capture chromosome conformation capture (Capture-C) and RNA sequencing, we identified genes on the same and different chromosomes as targets regulated by the enhancer. (
  • Furthermore, we show that expression of individual candidate target genes in an enhancer-deleted cell line rescued different aspects of tumorigenesis. (
  • Our data suggest that the rs55958994-associated enhancer affects prostate cancer progression by influencing expression of multiple genes via long-range chromatin interactions. (
  • Unlike genes, they do not code for human proteins or carry hereditary traits, but are among the complement of DNA elements that play a role in turning genes on and off. (
  • All cell nuclei within an individual contain the same set of genes, some of which may or may not be switched on by regulatory elements also written in DNA code. (
  • Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging. (
  • Here, we identify two cis-regulatory elements (E1 and E2) functioning as shadow enhancers to regulate the early expression of the HoxA genes. (
  • Simultaneous deletion of these shadow enhancers in embryonic stem cells leads to impaired activation of HoxA genes upon differentiation, while knockdown of a long noncoding RNA overlapping E1 has no detectable effect on their expression. (
  • Instead, we demonstrate that SET1A/COMPASS is required for full transcriptional activation of multiple Hox genes but functions independently of the E1 and E2 cis-regulatory elements. (
  • These genome elements are present in all cells, and normally are used by cells to turn on genes. (
  • The authors have analysed SHOX enhancer regions in a large cohort of short stature patients to study the importance of regulatory regions in developmentally relevant genes like SHOX . (
  • Called "tissue regeneration enhancer elements" or TREEs, these sequences can turn on genes in injury sites and even be engineered to change the ability of animals to regenerate. (
  • Yet, Poss says, what has not been explored are the regulatory elements that turn these genes on in injured tissue, keep them on during regeneration, and then turn them off when regeneration is done. (
  • It was already well known that small chunks of sequence, called enhancer elements, control when genes are turned on in a developing embryo. (
  • In the process, Kang discovered that the element could be separated into two distinct parts: one that activates genes in an injured heart, and, next to it, another that activates genes in an injured fin. (
  • The rocG gene of Bacillus subtilis , encoding a catabolic glutamate dehydrogenase, is transcribed by SigL (σ 54 )-containing RNA polymerase and requires for its expression RocR, a member of the NtrC/NifA family of proteins that bind to enhancer-like elements, called upstream activating sequences (UAS). (
  • In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. (
  • Each enhancer element contains binding sites for upstream segmentation gene products such as Bicoid and Kruppel (which, as you will recall, are themselves transcription factors). (
  • The specificity of the enhancers can be demonstrated by removing just one of them (the element that specifies stripe 2, say) and inserting it upstream of a reporter gene like the bacterial beta-galactosidase (Bgal). (
  • Additionally, sequence variation at C/EBP site I, which lies immediately upstream of the distal nuclear factor kappa B site and immediately downstream of a binding site for activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB), has been shown to affect HIV-1 long terminal repeat (LTR) activity. (
  • The characterized promoter fragment would be an ideal candidate for genetic engineering and seeking of upstream trans -acting elements. (
  • An enhancer may be located upstream or downstream of the gene it regulates. (
  • The proximal sequence upstream of the gene that tends to contain primary regulatory elements is a proximal promoter. (
  • Enhancer elements in the viral upstream regulatory region positively regulate this promoter. (
  • Finally, we mapped elements in the region of p742 that confer responsiveness to differentiation and show that the upstream regulatory region does not contribute to the differentiation response of p742. (
  • The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia. (
  • In S. cerevisiae , upstream activation sequences (UASs) are generally located within a few hundred base pairs of a target gene, while in Drosophila and mammals, enhancers are often several kilobases away. (
  • Another significant difference between yeast and metazoans concerns yeast upstream activation sequences (UASs) and their metazoan counterparts, enhancers. (
  • Chromatin insulators, or boundary elements, appear to control eukaryotic gene expression by regulating interactions between enhancers and promoters. (
  • It has been proposed that eukaryotic chromatin is organized into functionally independent domains to prevent illegitimate enhancer-promoter communication. (
  • Although sequence conservation as a result of functional constraint has been a useful property to identify transcriptional enhancers, this identification process has been advanced through the development of techniques such as ChIP-seq and chromatin conformation capture technologies. (
  • Methods We performed conditional analysis on genetic association data and used epigenetic data on chromatin remodelling and transcription factor (TF) binding to identify the primary AS-associated IL23R-IL12RB2 intergenic SNP. (
  • Here, we utilize global chromatin occupancy analyses to demonstrate that robust YAP binding is restricted to a relatively small number of distal regulatory elements in the genome. (
  • The movement of enhancers and promoters in and out of higher-order chromatin structures within the nucleus are associated with changes in expression and histone modifications.However, the factors responsible for mediating these changes and determining enhancer:promoter specificity are still not completely known.In this review, we summarize what is known about the patterns of epigenetic and chromatin features characteristic of elements involved in long-range interactions. (
  • The movement of enhancers and promoters in and out of higher-order chromatin structures within the nucleus are associated with changes in expression and histone modifications. (
  • In this review, we summarize what is known about the patterns of epigenetic and chromatin features characteristic of elements involved in long-range interactions. (
  • a) An active chromatin hub (ACH) is a structure that allows enhancers and promoters to come into close spatial proximity with each other (40). (
  • These chromatin structures depend on sequence-specific TFs bound to both the enhancer and promoter and thus can explain the specificity observed in enhancer:promoter interactions. (
  • Interactions between regulatory elements separated by large genomic distances have been observed at high frequencies at other loci, leading to the proposition that chromatin looping generally results in the formation of hub-like structures. (
  • These active chromatin hubs (ACH) are responsible for bringing enhancers and promoters into close spatial proximity as well as providing an environment that is transcriptionally permissive (Figure 3a). (
  • It is now well evidenced that these enhancers contact promoters with looping of in-between chromatin. (
  • In eukaryotic cells the structure of the chromatin complex of DNA is folded in a way that although the enhancer DNA is far from the gene in regard to the number of nucleotides, it is geometrically close to the promoter and gene. (
  • Comparative genomic analyses uncovered evolutionarily conserved consensus-binding sites within this element, which chromatin immunoprecipitation and electrophoretic mobility shift assays confirm are bound by Hand2 and Phox2b. (
  • One mechanism, looping, stipulates that proteins bound at an enhancer associate directly with proteins bound at a core promoter with a looping out of the intervening chromatin. (
  • Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. (
  • The genetic and restriction maps of the rocG locus and some of the plasmids used in this study are presented in Fig. 2 . (
  • Our work sheds light on the process of gene regulatory evolution by showing how a locus can undergo enhancer turnover and nevertheless maintain the ancestral transcriptional output. (
  • Historically, enhancers were the first elements found to act at-a-distance from the gene, as exhaustively reviewed by Palstra and Grosveld (2012) , starting from the β-globin locus, a model for cellular differentiation. (
  • Transcriptional regulatory elements such as locus control regions, enhancers or insulators act by repositioning specific genetic loci to regions with active or silent transcription 6 . (
  • Starting with 16 AD risk variants located in enhancers, the DNA regions that influence transcription, the researchers linked each locus to changes in expression of a downstream gene that correlated with AD risk. (
  • In eight enhancers, the authors pinpointed the functional variant for a GWAS risk locus. (
  • We used linear regression to test the associations between methylation scores at 461?281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. (
  • Global Genetic Architecture of an Erythroid Quantitative Trait Locus, HMIP-2. (
  • Additive Variance Calculator and Genetic Variance from a Single Locus . (
  • In Brassica spp, SI is controlled sporophytically by a single Mendelian genetic locus, the S locus ( Bateman, 1955 ). (
  • Transposon-induced variegation traits are powerful genetic tools to study gene expression and regulation ( 2 ). (
  • Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). (
  • Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis -acting regulators of tissue-specific gene expression programs. (
  • Relevant objectives of the first part of the course are to provide content concerning the organization of the human genome and the genetic and epigenetics mechanisms involved in genome mutation and in control of gene expression. (
  • Enhancers mediate the transcriptional regulation of gene expression, enabling isogenic cells to exhibit remarkable phenotypic diversity ( Davidson and Peter 2015 ). (
  • The CisRegVar project sets out to address how genetic variation (in cis-regulatory elements) affects transcription factor binding and gene expression during embryonic development. (
  • We quantified RNA levels in embryos collected from 82 genotypes (DGRP lines) at three developmental stages during embryonic development and assessed the impact of genetic variation on gene expression. (
  • Taken together, these studies show that genetic variation (1) has a substantial impact on gene expression variation during embryonic development, (2) impacts not only the levels, but also the specific transcript isoforms that are produced, creating a huge diversity at both the 5' and 3' ends of transcripts and (3) is partially buffered by extensive genetic epistasis within both enhancers and promoter elements. (
  • Translocations may affect the level of gene expression, or more commonly, these genetic abnormalities may generate fusion or chimeric proteins with altered functional properties. (
  • This allowed them to examine how disease-associated genetic variants affect gene expression. (
  • Investigations into genetic and gene expression profiling, as well as single nucleotide polymorphism analyses, have helped to better understand the underlying molecular mechanisms of asthma. (
  • Remarkably, he found that borrowing these elements from the genome of zebrafish could activate gene expression in the injured paws and hearts of transgenic mice. (
  • These DNA sequences are functionally characterized by two properties: they prevent enhancer-promoter interactions and buffer transgenes from the chromosomal-position effects of genomic sequences adjoining the transgene insertion site ( 11 , 14 , 22 , 23 , 36 , 42 , 43 ). (
  • Repetitive noncoding DNA sequences also form satellite DNA, which is a part of other structural elements. (
  • First, genetic data indicate that these sequences are not millions of years old. (
  • Compared with coding regions, which are generally highly constrained by protein structure and function, enhancers are freer to evolve, because TFBSs are small (6-10 nucleotides long) and accept much higher levels of sequence divergence than the genetic code, i.e. each transcription factor can recognize a variety of binding site sequences. (
  • The regulatory sequences include the promoter region together with enhancer elements. (
  • Many of those sequences were located in gene deserts, which are in fact so clogged with regulatory DNA elements that they have recently been renamed regulatory jungles . (
  • Hundreds of retrovirus-like sequences have features that suggest they might be gene enhancers, but only a small fraction displays gene-regulating activity in experiments on mouse stem cells. (
  • and (b)DNA sequences that are degenerate as a result of the genetic code to a DNA sequence of (a). 2. (
  • Transcription factors are proteins that bind to specific DNA recognition sequences in the promoter or enhancer elements of a gene. (
  • 26%) involved only enhancer sequences residing a considerable distance away from the gene. (
  • 45%) involve enhancer sequences and leave the SHOX gene intact. (
  • We are just at the beginning of this work, but now we have an encouraging proof of concept that these elements possess all the sequences necessary to work with mammalian machinery after an injury," said Poss. (
  • Some prevent enhancers from aiding in transcription (enhancer-blocker insulators). (
  • Some insulators can function as both an enhancer blocker and a barrier. (
  • Other elements, such as insulators, assist this process. (
  • However, the frontier between the different classes: (1) promoters/proximal elements, (2) enhancers, (3) insulators, are not clearly defined. (
  • Once thought to only act by counteracting the spread of heterochromatin like some insulators, it also operates like classical enhancers by contacting promoter with specific factors (EKLF, GATA-1, FOG-1) and looping. (
  • These include enhancers, silencers and barrier insulators to name but a few. (
  • Boundary elements such as Mcp, Fab-7, and Fab-8 and adjacent silencers flank the iab domains and restrict the activity of the iab enhancers. (
  • Like enhancers, silencers can be found before or after the gene they control and can be some distance away on the DNA strand. (
  • There are promoters, enhancers, silencers and many other functional DNA bits. (
  • Finally, we also report differential recruitment of TFIID and other GTFs at promoters and enhancers. (
  • Interactions between promoters and enhancers and represented by dashed lines. (
  • Neuberger's elucidation of these classes of antibody diversity began in a collaboration with Milstein to create transgenic mice as tools to define the role of promoters and enhancers in the somatic hypermutation of antibody gene loci. (
  • However, the factors responsible for mediating these changes and determining enhancer:promoter specificity are still not completely known. (
  • Human and chimpanzee-induced pluripotent stem cells show limited species-specificity in transposable element silencing. (
  • Mutations in regulatory regions including enhancers are an important source of variation and innovation during evolution. (
  • their malfunction through point mutations in either regulatory elements or factors modulating enhancer-promoter communication could result in development problems. (
  • The near base-pair resolution obtained by 3'Tag seq allowed us to pinpoint causal mutations in enhancers, RNA motifs and transcription factor binding sites. (
  • By 1998, Milstein, Cristina Rada, and Neuberger noticed that certain genetic models could separate intronic mutations into discrete phases: an agent that caused G:C mutations and one that caused A:T mutations. (
  • Bodine added, "I believe our study is the first of many studies that will show that mutations in barrier insulator elements are responsible for numerous inherited and acquired diseases, including cancers. (
  • A UAS placed downstream of the promoter or even on a separate, catenated, plasmid DNA retains its functional activity in an in vitro assay ( 8 , 9 ), but no functional bacterial enhancer-like element has yet been found to have a natural location far downstream of the promoter it regulates, despite the fact that this is a common feature of eukaryotic enhancers ( 1 ). (
  • The third boundary element identified, Mcp, preserves the functional autonomy of the iab - 4 and iab - 5 cis -regulatory domains ( 19 , 20 , 24 ). (
  • The identity of regulatory elements and other functional regions in noncoding DNA is not completely understood. (
  • The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. (
  • By targeted mutagenesis experiments, we disrupted these EY and TOY binding sites and studied their functional involvement in the so10 enhancer expression in the eye progenitor cells. (
  • Overall, our data indicates that genetic variants can easily generate non-coding transcription (often with very complex expression patterns) - these will be classified as lncRNAs, but generally reflect by-stander non-functional expression. (
  • We present a novel algorithm, Prioritization And Functional Assessment (PAFA), that prioritizes and assesses the functionality of genetic variants by introducing population differentiation measures and recalibrating training variants. (
  • Fully functional regulatory elements can arise rapidly from transposable elements via a novel route where non-allelic gene conversion can act to speed up the evolutionary fine-tuning of regulatory elements. (
  • A new approach combines guide RNA multiplexing with CRISPR activation and interference to facilitate functional studies of transposable elements present in hundreds of copies throughout the human genome. (
  • Lower panel shows sgRNA cleavage sites inside the 98-bp core enhancer. (
  • D ) ATP2B4 expression in HUDEP-2 cells with 98-bp core enhancer deletion. (
  • E ) ATP2B4 expression in HUDEP-2 cells with individual sgRNAs specifying cleavages within the 98-bp core enhancer. (
  • Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer. (
  • Here, we show that these four enhancer regions also contribute to bcl-2 up-regulation in t(14;18) cells. (
  • Nuclear factor κB binding sites were shown to be primarily responsible for the positive activity contributed by the HS1,2 and HS4 regions, and we observed the in vivo interaction of these factors with the human immunoglobulin heavy chain gene enhancer regions in t(14;18) cells. (
  • We have previously described that hypothalamic Pomc expression in mammals is controlled by two enhancers-nPE1 and nPE2-that are derived from transposable elements and that presumably replaced the ancestral neuronal Pomc regulatory regions. (
  • The enhancer regions are found at a distance from the promoter, to either the5' or 3' sides of the gene or within introns. (
  • If so, AD risk variants might preferentially occur in regulatory regions, such as enhancers and promoters, that are active in these cells, the authors reasoned. (
  • In the first, they made use of the fact that enhancer regions physically bind promoters, the DNA regions that initiate gene transcription (see image above). (
  • Psychiatric disease variants tend to cluster in regulatory regions active in neurons, while AD risk variants lie predominantly in microglial enhancer elements. (
  • These elements may be found in both promoter and enhancer regions. (
  • Compared with cells in non-cancerous and tumor-derived organoids, those in metastatic ones displayed an extraordinary number of alterations in regions called enhancers. (
  • Modifications to histone proteins (green and red dots) mark active enhancers, where a transcription complex (colored circles) assembles on a chromosome. (
  • We propose that enhancer sharing occurs widely across eukaryotes, test key aspects of this hypothesis in Caenorhabditis elegans , and analyze its implications in other genomic phenomena. (
  • The study was hypothesis-free, that is, we cast a net across the entire genome allowing statistical significance to point us to a genetic variant, regardless of whether it fell in a genomic desert or an important gene. (
  • See also Grosse & Khoury, 2006 for the clinical utility of genetic testing, Offit, 2008 for issues surrounding genomic disease profiling, and Pharoah, 2008 for the possible utility of genomic profiling in breast cancer risk assessment. (
  • Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. (
  • The vast majority of TEs originate from retrotransposition of genetic elements known as short and long interspersed nuclear elements, long terminal repeat-superfamilies and direct transposition of TE-containing genomic DNA. (
  • 6 7 Larger deletions and insertions have been described, as well as genomic rearrangements resulting from recombinations mediated by Alu elements which cause inappropriate exon splicing. (
  • The strongest evidence for this mechanism comes from analysis of a bacterial enhancer-like element ( 32 ). (
  • They specifically would like to explore targeting the 6q HBS1L-MYB intergenic enhancers as a genetic therapeutic approach for reactivating fetal hemoglobin. (
  • These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. (
  • Based on the high frequency of somatic and germinal reversions of y-cs to Y (23%), it has been postulated that the y-cs phenotype may result from the presence of a transposable element in the Y gene ( 10 - 12 ). (
  • Systematic search for enhancer elements and somatic allelic imbalance at seven low-penetrance colorectal cancer predisposition loci. (
  • Enhancer elements and enhancer-binding proteins are widespread components of transcriptional regulation systems in eukaryotes ( 1 ). (
  • Enhancers provide binding sites for proteins that help activate transcription. (
  • We further studied the regulation of this element and found that both Drosophila Pax6 proteins namely EY and TOY bind and positively regulate so10 expression through different binding sites. (
  • Enhancers do not act on the promoter region itself, but are bound by activator proteins. (
  • Recent observations have shown two CCAAT/enhancer binding protein (C/EBP) binding sites to be critically important for efficient human immunodeficiency virus type 1 (HIV-1) replication within cells of the monocyte/macrophage lineage, a cell type likely involved in transport of the virus to the brain. (
  • Previous studies reported that CCAAT/enhancer binding protein β (C/EBP β) can transactivate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in transient transfection analyses and that the LTR contains three binding sites for this protein ( 39 ). (
  • Conclusions The rs11209032 SNP downstream of IL23R forms part of an enhancer, allelic variation of which may influence Th1-cell numbers. (
  • A1BG is not transcribed by a downstream enhancer box. (
  • These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. (
  • In addition, downstream promoter elements, widely used in metazoans, are not found in S. cerevisiae ( 40 ). (
  • She found that active myeloid enhancers contained a disproportionate number of AD risk loci. (
  • Through genetic studies, she has identified segments of DNA, called quantitative trait loci, on chromosome 11p (where the beta globin gene is located), chromosome 6q, and the BCL11A gene on chromosome 2p that are involved in stimulating HbF production in adults. (
  • Through her research, Dr. Thein hopes to eventually delineate the genetic architecture of fetal hemoglobin control in adults and identify the loci and sequence variants that account for disease variance among individual adults. (
  • A major finding of this study is that the genetic loci associated with asthma are enriched in epigenetic marks characterizing gene enhancers. (
  • Meta-analyses of genome-wide association studies conducted in these ethnically-diverse populations identified a total of 878 genetic variants belonging to 18 loci associated with asthma risk. (
  • Association of eleven common, low-penetrance colorectal cancer susceptibility genetic variants at six risk loci with clinical outcome. (
  • Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. (
  • We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. (
  • To understand the properties of eRNA expression for enhancer and promoter function, we developed a dual transgenic assay to simultaneously measure enhancer and promoter activities. (
  • We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. (
  • This work led to the identification and characterization of transcriptional enhancers that control antibody gene rearrangement, expression, and hypermutation. (
  • Finnegan DJ, Fawcett DH (1986) Transposable elements in Drosophila melanogaster . (
  • In: Lambert ME, McDonald JF, Weinstein IB (eds) Eukaryotic transposable elements as mutagenic agents. (
  • Hoover KK, Chien AJ, Corces VG (1993) Effects of transposable elements on the expression of the forked gene of Drosophila melanogaster . (
  • [16] Then, in the early 1950s, Barbara McClintock published a series of papers describing the existence of transposable elements , which are now recognized to be among the most successful selfish genetic elements. (
  • [17] The discovery of transposable elements led to her being awarded the Nobel Prize in Medicine or Physiology in 1983 . (
  • Cs1 is the first active transposable element isolated from sorghum. (
  • Transposable elements as causative agents of variegation and genetic variation were first discovered in maize by Barbara McClintock in the 1940s ( 1 ) and since have been found in many organisms. (
  • Although variegation mutants have been described in at least 35 plant species ( 3 ), active transposable elements have been isolated from only a minority of these plants. (
  • The P1-vv allele specifies variegated kernel pericarp pigmentation, and this allele contains an Ac transposable element insertion in the P1-rr gene. (
  • The transposon is named Candystripe1 ( Cs1 ) and is a member of the CACTA family of plant transposable elements. (
  • Transposable elements (TEs) are major components of eukaryotic genomes. (
  • Fine mapping of transposable element presence/absence variation amongst 216 Arabidopsis strains uncovers widespread novel genetic diversity that underlies differences in transcription and DNA methylation patterns. (
  • Soon after fertilisation, a critical portion of the embryonic genome is switched on through the actions of maternally inherited Stella, in part through controlling the activation of transposable elements. (
  • Population genomics in Arabidopsis thaliana uncovers an extensive repertoire of active transposable element families at the species level and reveals their importance as a source of rare alleles with large effects. (
  • However, the recent identification of novel regulatory functions for transposable and transposed genetic elements (TEs) may be an important and new key to help understand the genetics that cause the heterogeneous manifestations of the asthma pathology. (
  • The role of variation in gene regulatory elements in the cardiac conduction system has recently been demonstrated by studies on enhancers of SCN5A/SCN10A and TBX5. (
  • As argued in part 3 of this series of articles, ERVs may be the executors of genetic variation, and qualify as specifically designed variation-inducing genetic elements (VIGEs) responsible for variation in higher organisms. (
  • The idea that mobile genetic elements are involved in creating variation is not new. (
  • 1 It is only recently that we have begun to understand the power of VIGEs (variation-inducing genetic elements) as genetic regulators and switches. (
  • CISREGVAR (Cis-regulatory variation: Using natural genetic variation to dissect cis-regulatory control of embryonic development. (
  • Despite a considerable degree of genetic variation, embryos develop in a stereotypic manner. (
  • Our results uncover context-specific effects of genetic variation at specific embryonic stages and identifies mechanisms that buffer these effects to ensure robustness within developmental programs. (
  • Human genetic variation is a major resource in forensics, but does not allow all forensically relevant questions to be answered. (
  • 991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). (
  • This work suggests that noncoding RNAs active in dopamine neurons are a primary link between genetic variation and neurodegenerative and neuropsychiatric diseases affecting dopamine neurons in our brains," Dr. Scherzer said. (
  • The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. (
  • Genetic and epigenetic editing experiments establish causal links between transposon-derived enhancers and gene regulation in mouse embryonic and extraembryonic lineages. (
  • We reported previously that the lymphocyte-derived octamer transcription factor 2A (Oct-2A or OTF-2A) activated both natural immunoglobulin promoters and synthetic promoters which contain the 'octamer' site, but was unable by itself to stimulate transcription from a remote enhancer position. (
  • Enhancers can evolve by changes in the sequence, arrangement and repertoire of transcription factor binding sites, but whole enhancers can also be lost or gained in certain lineages in a process of turnover. (
  • Thus, we defined thousands of candidate enhancer elements by incorporating these features, and found that they have a significant propensity to be bound by p300, an enhancer binding transcription factor. (
  • We also identify the neuronal regulatory region of zebrafish pomca and confirm that it is not homologous to the mammalian enhancers. (
  • One of these was how the long-range activation potential of eukaryotic enhancers could be restricted to the relevant target promoter. (
  • Taking advantage of the huge RNA-Seq datasets generated during the course of this project, we also identified long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) that are transcribed during these stages of embryogenesis. (
  • Using a novel technique called laser microdissection, investigators observed that noncoding RNAs active in dopamine neurons are a surprising link between genetic risk, Parkinson's, and psychiatric disease. (
  • These clusters of noncoding DNA elements were expressing enhancer RNAs that are linked to several genetic risk variants for PD, the researchers found. (
  • We think that these risk variants target the enhancer RNAs active in dopamine neurons. (
  • Corces VG, Geyer PK (1991) Interactions of retrotransposons with the host genome: the case of the gypsy element of Drosophila . (
  • Dickson B, Hafen E (1993) Genetic dissection of eye development in Drosophila . (
  • The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. (
  • Enhancer elements are essential for tissue-specific gene regulation during mammalian development. (
  • Together, these data define a tissue-specific Hand1 cis -regulatory element controlled by two factors essential for the development of the sympathetic nervous system and provide in vivo regulatory evidence to support previous findings that Hand2, rather than Hand1, is predominantly responsible for regulating TH, DBH, and Hand1 expression in developing sympathetic neurons. (
  • We observed that these promoter-interacting hotspots significantly overlap with known enhancer-associated histone modifications and DNase I hypersensitive sites. (
  • Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. (
  • The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. (
  • F) Histogram indicating the fraction of YAP− or YAP+ enhancers catalogued as regular o super- enhancers in HuCCT1 cells. (
  • In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). (
  • Erythroid cells with a deletion of the ATP2B4 enhancer had abnormally high intracellular calcium levels. (
  • Nondeletion ( n = 13), monoallelic deletion ( n = 13), and biallelic deletion ( n = 14) are clones with, respectively, 0, 1, or 2 ATP2B4 enhancer alleles deleted. (
  • C ) ATP2B4 expression in 293T cell clones exposed to enhancer targeting sgRNA pairs, but without deletion ( n = 4) or with biallelic deletion ( n = 3). (
  • The LCR enhancer, of which the deletion leads to thalassemia, conversely illustrates this ambiguity. (
  • Finer deletion analysis identified an enhancer element existing as a tandem repeat in the promoter region between -574 to -513 bp and conferring strong promoter activity. (
  • Deletion of this enhancer from prostate tumor cells resulted in decreased tumor initiation, tumor growth, and invasive migration, as well as a loss of stem-like cells. (
  • An integrated encyclopedia of DNA elements in the human genome. (
  • Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. (
  • High-throughput identification of long-range regulatory elements and their target promoters in the human genome. (
  • When it was discovered that more than half of the human genome consists of (remnants of) mobile elements, McClintock's ideas were revived and further developed by Roy Britten and Eric Davidson. (
  • A team led by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), and Yale University School of Medicine, report on their findings in the early online issue of the Nov. 22, 2010, Journal of Clinical Investigation , marking the first time that a human disease is known to be caused by a defect in this otherwise poorly understood element in the genome. (
  • Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. (
  • The promoter region of this LMO consists a duplicated enhancer region from the cauliflower mosaic virus 35S promoter combined with the promoter of the act1 gene, that encodes Actin 1, from Oryza sativa . (
  • The MYB-QKI fusion gene causes cells to make a protein that binds to another control element - a promoter - that also revs up MYB activity, prodding the cells into runaway growth. (
  • These results suggest that the interactions of the nuclear factor κB and Sp1 transcription factors with the immunoglobulin heavy chain enhancer region are important for bcl-2 deregulation in t(14;18) cells. (
  • Such interactions are possible because of the flexible nature of DNA which allows the enhancers to come close to the promoter by looping out the DNA in between (see diagram below). (
  • In erythoid cells, where β-globin is expressed, these interactions form a compartment containing regulatory elements that has a high level of transcriptional activity (40). (
  • Knock out of TFs responsible for regulating β-globin expression (EKLF and GATA-1) result in the loss of interactions between the gene and its enhancers, leading to loss of the overall hub-like structure (163,164). (
  • In total, our study presents a novel high-throughput workflow for confident, genome-wide discovery of enhancer-target promoter pairs, which will significantly improve our understanding of these regulatory interactions. (
  • Given that enhancer-promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. (
  • We experimentally show that nonspecific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. (
  • Parkinson's disease (PD), like most common disorders, involves interactions between genetic make-up and environmental exposures that are unique to each individual. (
  • Cataloguing enhancer-promoter interactions in the four major cell types of the brain, researchers found that Alzheimer's risk variants predominantly appeared in microglial enhancers. (
  • Using probes from the maize p1 gene that cross-hybridize with the sorghum Y gene, we isolated the y-cs allele containing a large insertion element. (
  • Furthermore, the risk variant of the allele abrogated enhancer function in both cases. (
  • The Gbx2 cre/ER allele expresses a CreER T2 -internal ribosome entry site (IRES)-enhanced green fluorescent protein (EGFP) cassette from the Gbx2 promoter/enhancer elements. (
  • de Laat, W. & Duboule, D. Topology of mammalian developmental enhancers and their regulatory landscapes. (
  • Interestingly, many QTLs showed genetic epistasis within developmental enhancers. (
  • Short stature is a developmental, multifactorial condition with a strong genetic component. (
  • We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation. (
  • The authors conclude that enhancer deletions in the SHOX gene region are a relatively frequent cause of growth failure in patients with idiopathic short stature and Leri-Weill syndrome. (
  • The proline-rich activation domains of AP-2 and CTF/NF1 may represent a third class with considerable promoter activity and low but significant enhancer activity. (
  • ZRE-B can be deleted without affecting the R-dependent enhancer activity. (
  • The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex. (
  • Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. (
  • The enhancers are able to individually or in combination activate bcl-2 promoter activity. (
  • The HS4 enhancer region was found to impart the largest positive effect on the bcl-2 promoter, activating it by 6-fold, whereas addition of the HS1,2 region with HS4 increased promoter activity by approximately 9-fold. (
  • In addition, two Sp1 binding sites in HS4 were also found to positively influence bcl-2 activity, and Sp1 was observed to interact with the human HS4 enhancer in vivo . (
  • In conclusion, this study elucidates the expression characteristics of the LCYb1 promoter from citrus and further identifies a novel enhancer element required for the promoter activity. (
  • Transgenic analysis revealed a relationship between the direction of eRNA transcription and its enhancer or promoter activity. (
  • Strong promoters generally have no enhancer activity. (
  • These results suggest that the level of either promoter or enhancer activity from a regulatory element is reflected in the directionality and levels of eRNA transcription. (
  • In this report, we mapped viral DNA elements that control transcriptional activity from p742. (
  • The region containing the transcriptional start sites is dispensable for activity, and at least two separate elements in the E6/E7 region are capable of supporting transcription. (
  • Epigenetic control elements called enhancers are "hijacked" and brought closer to the MYB gene, which increases MYB activity. (
  • Mutational analyses revealed that the conserved Phox2 and E-box binding sites are necessary for proper cis -regulatory element activity, and expression analyses on both Hand2 conditionally null and hypomorphic backgrounds demonstrate that Hand2 is required for reporter activation in a gene dosage-dependent manner. (
  • accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. (
  • Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders. (
  • YAP modulates transcription from these elements predominantly by regulating promoter-proximal polymerase II (Pol II) pause release. (
  • Recurrent tandem duplications intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. (
  • Researchers are working to understand the location and role of these genetic components. (
  • Researchers show that genetic enhancer elements likely contribute to face shape in mice. (
  • For eight of the 16 enhancers, the researchers pinpointed the specific genetic change that affected expression. (
  • BOSTON, MA (Feb. 1, 2016) - Diagnosis and treatment decisions for a recently recognized type of children's brain tumor should be improved by the discovery of the genetic mechanism that causes it, say researchers who identified the unusual DNA abnormality in angiocentric gliomas. (
  • In the current study, the researchers analyzed data from 249 PLGG tumors, including 19 angiocentric gliomas, and discovered an unusual genetic accident as the fundamental cause of the angiocentric gliomas. (
  • Finally, the researchers tested whether these "tissue regeneration enhancer elements" or TREEs could have a similar effect in mammalian systems like mice. (
  • February 1, 2016) -- Diagnosis and treatment decisions for a recently recognized type of children's brain tumor should be improved by the discovery of the genetic mechanism that causes it, say researchers who identified the unusual DNA abnormality in angiocentric gliomas. (
  • When the supplementary transcription factors bound to enhancer elements interact with the basal machinery, it is like putting the engine into gear and pulling away from the kerb. (
  • This movement allows enhancers to interact with targets that were previously held in the repressive domain. (
  • Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. (
  • We demonstrate that, although Hand2 and Hand1 interact with Phox2b identically in vitro , Hand1 and Hand2 display different binding affinities for the conserved E-boxes within the Hand1 SG enhancer. (
  • By studying identical twins, who share very similar DNA, Dr. Thein's lab has demonstrated that HbF levels are predominantly genetically controlled, and that almost 90 percent of the difference in HbF levels from person to person can be accounted for by differences in genetic background, both outside and within the environment of the beta globin gene. (
  • Plank JL, Dean A. Enhancer function: mechanistic and genome-wide insights come together. (
  • We further discuss implications of the observed difference between normal growth control and cancer for drug development, and the inherent features of genome-wide association studies that may specifically lead to identification of disease-specific regulatory elements. (
  • Observations of what is now referred to as selfish genetic elements go back to the early days in the history of genetics . (
  • In evolutionary genetics, additive genetic variance ( V A ) is a measure for the potential amount of evolutionary change caused by natural selection. (
  • Proximal' activation domains, exemplified by glutamine-rich domains of Oct-1, Oct-2A and Sp1, stimulate transcription only from a position close to the TATA box, usually in response to a remote enhancer. (
  • The same level of white activation was observed when the Mcp element combined with the insulator alone was interposed between the eye enhancer and the promoter, suggesting that the insulator is responsible for the interaction between the Mcp elements. (
  • In this study, we describe the activation of the bcl-2 promoter by the immunoglobulin heavy chain gene 3′ enhancers. (
  • Enhancer region HS4 is the most active with the bcl-2 promoter, and different combinations of the 3′ enhancers show increased activation of bcl-2 expression. (
  • FOXA1 activation, inducing enhancer reprogramming that endows a cancer cell with metastatic properties, is an epigenetic mechanism, as opposed to a genetic one, that explains at least one mechanism of metastasis in this form of pancreatic cancer, and likely, other cancer types as well. (
  • Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. (
  • Genome editing at the ATP2B4 erythroid enhancer. (
  • The interaction between the Mcp elements, each containing the insulator and PRE, allows the eye enhancer to activate the white promoter over the repressed yellow domain. (
  • After all, it's theoretically possible that an enhancer, even one located megabases away, could reach out and activate a distant but otherwise silent promoter. (

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