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
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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 ...
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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,
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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.
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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 ...
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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
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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 ...
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Dive into the research topics of Motor neuron-expressed microRNAs 218 and their enhancers are nested within introns of Slit2/3 genes. Together they form a unique fingerprint. ...
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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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 ... The future of genetic codes and BRAIN codes (Dr. Church's seminar at the NIH on February 8, 2017) (All articles with dead ... 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 ...
cis-regulatory element Enhancer (genetics) Epistasis Genetic correlation Metabolic network Metabolic supermice Polygene Paaby, ... Most genetic traits are polygenic in nature: controlled by many genetic variants, each of small effect. These genetic variants ... Sickle cell anemia is a genetic disease that causes deformed red blood cells with a rigid, crescent shape instead of the normal ... One measure of pleiotropy is the fraction of genetic variance that is common between two distinct complex human traits: e.g., ...
... which is responsible for suppressing an upstream enhancer element known as hs1473. When H2AFY is removed, the enhancer is ... 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 ... Liebenberg Syndrome is a result of one of two different genetic mutations. The first is a deletion upstream of the PITX1 gene ...
... 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 ...
... "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 ... The patterning of Drosophila wings has long been of interest to evolutionary biologists as understanding the genetic changes ...
Some cases of polydactyly are caused by mutations in the ZRS, a genetic enhancer that regulates expression of the sonic ... a mutation of the cis-regulatory element ZRS (ZPA regulator sequence) is associated. ZRS is a noncoding element, 800 ... Genetic work studying the DNA basis of the condition indicates that many different mutations in the same ZRS area can all lead ... The SHH protein is an important signalling molecule involved in patterning of many body elements, including limbs and digits. ...
... 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 ... Description of background on D. guttifera use in genetic studies in the Drosophila quinaria species group article. Wing ...
Long interspersed nuclear elements (LINEs) are typically 3-7 kilobases in length. Short interspersed nuclear elements (SINEs) ... When TEs are introduced into a new host, such as from a virus, they increase genetic diversity. In some cases, host organisms ... In the 2000s, the data from full eukaryotic genome sequencing enabled the identification of different promoters, enhancers, and ... Some repetitive elements are neutral and occur when there is an absence of selection for specific sequences depending on how ...
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: ...
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 ...
Tonegawa also discovered a transcriptional enhancer element associated with antibody gene complex, the first cellular enhancer ... Tonegawa's Nobel Prize work elucidated the genetic mechanism of the adaptive immune system, which had been the central question ... Gillies, S. D., Morrison, S. L., Oi, V. T., & Tonegawa, S. (1983). A tissue-specific transcription enhancer element is located ... In experiments beginning in 1976, Tonegawa showed that genetic material rearranges itself to form millions of antibodies. ...
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 ...
... genetic epistasis within enhancers and promoters, and extensive redundancy, which together contribute to canalization in ... genetics and computational biology approaches to functionally dissect the role of non-coding cis-regulatory elements in the ... Her group's research has uncovered a number of properties of enhancers and enhancer-promoter communication, including pre- ... in addition to mechanisms that allow enhancers to withstand the effects of genetic variation, including collective ...
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; ...
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 ...
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 ...
Enhancer+Elements,Genetic at the US National Library of Medicine Medical Subject Headings (MeSH) TFSEARCH JASPAR ReMap ENCODE ... 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 ...
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 ...
An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element". Science. 346 (6215): 1373-7. ... December 2015). "Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism". Nature. 528 (7582): ... Both super-enhancers and stretch enhancers are clusters of enhancers that control cell-specific genes and may be largely ... ROSE separates super-enhancers from typical enhancers by their exceptional enrichment in a mark of enhancer activity. Homer is ...
HS5 is thought to be a genetic insulator in vivo as it has both enhancer-blocking activity and transgene barrier activities. ... When they are located farther away from the promoter, insulator elements would compete with the enhancer and interfere with ... The specific way in which insulators block enhancers is dependent on the enhancers mode of action. Enhancers can directly ... An enhancer can also act on a promoter through a signal (tracking model of enhancer action). This signal may be blocked by an ...
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 ...
Chuong EB, Rumi MA, Soares MJ, Baker JC (March 2013). "Endogenous retroviruses function as species-specific enhancer elements ... The majority of ERVs that occur in vertebrate genomes are ancient, inactivated by mutation, and have reached genetic fixation ... In particular, both human class I and class II MHC genes have a high density of HERV elements as compared to other multi-locus- ... This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. There are indications ...
... s are members of the genetic vaccines, because they contain a genetic information (DNA or RNA) that codes for the ... Additional modifications to improve expression rates include the insertion of enhancer sequences, synthetic introns, adenovirus ... AC with 0 elements, DNA vaccines, DNA, Nucleic acid vaccines, Gene delivery, Virology, 21st-century inventions). ... These "genetic adjuvants" can be administered as a: mixture of 2 plasmids, one encoding the immunogen and the other encoding ...
... thereby reducing or eliminating the genetic variation of nearby loci within the population. selfish genetic element Any genetic ... Proximity to promoters, enhancers, and other regulatory elements, as well as to regions of frequent transposition by mobile ... mobile genetic element (MGE) Any genetic material that can move between different parts of a genome or be transferred from one ... mobilome The entire set of mobile genetic elements within a particular genome, cell, species, or other taxon, including all ...
Certain limb-enhancer sequences are also conserved between different types of appendage, such as limbs the phallus. For ... The limb's skeletal elements are prefigured by tight aggregates known as cellular condensations of the pre-cartilage ... The study of limb reduction and limb loss is unravelling the genetic pathways that control limb development. The Turing system ... It is thought that these cumulative changes in the snake ZRS are indicative of a progressive loss of function in this enhancer ...
She has also characterized the mechanisms of bridging promoter and enhancer elements within and between chromosomes. As stated ... Genetic predictors of disease can raise thorny ethical issues". Harvard Medicine. Ting Wu & Dana Waring. (2009). "The next ... and the mechanisms of bridging promoter and enhancer elements within and between chromosomes. She also studies ultra-conserved ... Morris JR, Chen J-l, Geyer PK, Wu C-t.; Chen; Geyer; Wu (1998). "Two modes of transvection: Enhancer action in trans and bypass ...
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 ...
There also exist virulence plasmids that contain the genetic elements necessary for bacteria to become pathogenic as well as ... Spacially, ecDNA hubs could cause intermolecular enhancer-gene interactions to promote oncogene overexpression. Rush MG, Misra ... SpcDNAs are derived from repetitive sequences such as satellite DNA, retrovirus-like DNA elements, and transposable elements in ... "Extrachromosomal genetic elements in Micrococcus". Applied Microbiology and Biotechnology. 97 (1): 63-75. doi:10.1007/s00253- ...
In addition, the transposon contained promoter and enhancer elements, a splice donor and acceptors to allow gain- or loss-of- ... Transposons as a genetic tool Transposable element Transposase Barbara McClintock "Feeding hungry mouths". Biotechnology ... A newer technique called shuttle mutagenesis uses specific cloned genes from the host species to incorporate genetic elements. ... In addition, other proteins seem to be able to bind with and affect the transposition of the IS50 elements, such as DnaA. The ...
Enhancers are regions of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene ... Promoters are important gene regulatory elements used in tuning synthetically designed genetic circuits and metabolic networks ... September 2020). "Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal ... insulators and tethering elements. Among this constellation of elements, enhancers and their associated transcription factors ...
During his career on the genetic causes of cancer, his laboratory team identified two genes (Mlf1 and Hls5) implicated in the ... 6787-6798 (2015) Transcriptional enhancers lead waves of co-ordinated transcription in transitioning mammalian cells. Science ... AC with 0 elements, 1953 births, Living people, University of Western Australia alumni, Australian scientists, Companions of ...
"Identification of nucleotides responsible for enhancer activity of sterol regulatory element in low density lipoprotein ... A multi-locus genetic risk score study based on a combination of 27 loci, including the LDLR gene, identified individuals at ... and a genetic disease". Proceedings of the National Academy of Sciences of the United States of America. 81 (9): 2826-30. ... "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary ...
... genetic carrier - genetic code - genetic drift - genetic engineering - genetic fingerprint - genetic recombination - genetics ... element - element symbol - ELISA - ELISPOT - embryo - embryonal development - emulsion - endergonic reaction - endodermis - ... enhancer - enkephalin - enthalpy - entomology - entropy - env gene product - environmental chemistry - enzyme - epidermal ... DNA transposable element - DNA virus - DNA-binding protein - dopamine D1 receptor - dopamine D2 receptor - dopamine receptor - ...
... is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the ... Giresi PG, Kim J, McDaniell RM, Iyer VR, Lieb JD (June 2007). "FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) ... Pennacchio LA, Bickmore W, Dean A, Nobrega MA, Bejerano G (April 2013). "Enhancers: five essential questions". Nature Reviews. ... FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements) requires as its first step crosslinking of the DNA with ...
January 2009). "Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter ... A study on genetic absence epilepsy rats from Strasbourg (GAERS) found that poor GABA uptake by GAT1 caused an increase in ...
Class II HDACs 5 and 9 inhibit the activity of a factor known as myocyte enhancer factor 2 (MEF2), which unable to bind ... Additionally, genes that encode for elements that prevent one type of cancer in a cell, may have altered function in another ... Due to genetic heterogeneity, environmental factors, and pathophysiological causes, individuals that exhibit similar disease ... Cells that carry loss-of-function mutations can be targeted by drugs that induce synthetic lethality, a genetic/protein ...
The (-13910) region, in particular, has been shown to function in vitro as an enhancer element capable of differentially ... Mattar R, de Campos Mazo DF, Carrilho FJ (2012). "Lactose intolerance: diagnosis, genetic, and clinical factors". Clin Exp ... functional role as a cis regulatory element". Hum. Mol. Genet. 12 (18): 2333-40. doi:10.1093/hmg/ddg244. PMID 12915462. ...
It binds to stress element promoters upstream of genes that are upregulated in the UPR. The aim of these responses is to remove ... It has been argued that the genetic and structural evidence supporting the model simply shows BiP dissociation to be merely ... An important example is that the proapoptotic protein CHOP (CCAAT/-enhancer-binding protein homologous protein), is upregulated ... The activated transcription factor upregulates UPR 'stress genes' by directly binding to stress element promoters in the ...
This genetic disease is caused by a malfunction in the HPRT1 gene, which clinically leads to the fatal uric acid urinary stone ... Specific items within each element carry a label of either E (essential) or D (desirable). Those labelled E are considered ... The further use of inhibitor-tolerant polymerases, polymerase enhancers with an optimized one-step RT-PCR condition, supports ... Prokaryotes, such as E. coli, lack the mRNA splicing mechanism of eukaryotes). RT-PCR can be used to diagnose genetic disease ...
... by IFN-gamma-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding ... Genetic Testing and Molecular Biomarkers. 13 (2): 223-6. doi:10.1089/gtmb.2008.0111. PMID 19371221. Mattila S, Tuominen H, ... This protein also has been shown to activate the transcription regulated by a gamma-interferon-activated transcription element ... "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics. 123 (4): 1116-23. doi: ...
Kim SH, Xia D, Kim SW, Holla V, Menter DG, Dubois RN (2010). "Human enhancer of filamentation 1 Is a mediator of hypoxia- ... and contains a retinoic acid response element (RARE) that is specifically bound by a retinoid X receptor (RXR)/retinoic acid ... "Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease". Neurosci. Lett. 477 (3): 121-3. ... Law SF, Estojak J, Wang B, Mysliwiec T, Kruh G, Golemis EA (1996). "Human enhancer of filamentation 1, a novel p130cas-like ...
... enhancer/silencer elements, or the local chromatin environment. These mutations can be associated with diseases or disorders ... April 2018). "Identification of novel putative causative genes and genetic marker for male sterility in Japanese cedar ( ...
The gene encodes for a transcription factor that belongs to the Hairy/Enhancer of Split (Hes) subfamily of basic helix-loop- ... This heterodimer binds to the E-Box promoter element, thereby promoting transcription of downstream genes such as Per and ... Jones CR, Huang AL, Ptáček LJ, Fu YH (May 2013). "Genetic basis of human circadian rhythm disorders". Experimental Neurology. ... Rossner MJ, Dörr J, Gass P, Schwab MH, Nave KA (1997). "SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled ...
A gene element, upstream of the previously thought exon 1 was originally thought to be an enhancer. In reality, this assumed ... evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes". Archives of Ophthalmology. 122 (1): 70-5 ... enhancer is the main promoter for this gene. The newly discovered intron 1 lies within and just near the end of the promoter ...
For example, miR16 contains a sequence complementary to the AU-rich element found in the 3'UTR of many unstable mRNAs, such as ... Zuo Y, Qiang L, Farmer SR (March 2006). "Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta ... Dimond PF (15 March 2010). "miRNAs' Therapeutic Potential". Genetic Engineering & Biotechnology News. 30 (6): 1. Archived from ... "microRNA response elements" on genes and pseudogenes and may provide another explanation for the persistence of non-coding DNA ...
In this regression, the observed two locus genetic effects are treated as dependent variables and the "pure" genetic effects ... 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. Ortlund EA, Bridgham ... Quantitative genetics focuses on genetic variance due to genetic interactions. Any two locus interactions at a particular gene ...
Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". ... "Genetic Switch" Theory Involving MITF and PAX3 in Proliferative and Invasive Phenotypes of Melanoma". review. Frontiers in ... of a new binding motif for the paired domain of Pax-3 and unusual characteristics of spacing of bipartite recognition elements ... August 2017). "PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability". primary. Cancer ...
found genetic evidence to support this result when they discovered that mPer1 mutants are not able to advance the clock in ... This CLOCK/CYCLE complex acts as a transcriptional activator for per and tim by binding to specific enhancers (called E-boxes) ... to form a negative element of the clock. This PER/CRY complex moves into the nucleus upon phosphorylation by CK1-epsilon ( ... Hao H, Allen DL, Hardin PE (July 1997). "A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster". ...
Over time the trauma and relationship to the victims typically evolve in a similar but more complicated way to genetic ... Whittle, Nigel; Singewald, Nicolas (2014-03-20). "HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: ... that is said to be an essential element of Korean identity by some, and a modern post-colonial identity by others. Michael D. ... Social, cultural, economic, and genetic mechanisms are intertwined in a complex manner. This results in significant hurdles in ...
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 ... Plant viruses can be used to engineer viral vectors, tools commonly used by molecular biologists to deliver genetic material ...
Transcription factor HES1 (hairy and enhancer of split-1) is a protein that is encoded by the Hes1 gene, and is the mammalian ... Votruba M, Payne A, Moore AT, Bhattacharya SS (1998). "Dominant optic atrophy: exclusion and fine genetic mapping of the ... This suggests that alternating HES1 levels may prompt differences in characteristics between anatomical elements of the central ... Grbavec D, Lo R, Liu Y, Stifani S (December 1998). "Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila ...
Human Genetic Variation". Science. 318 (5858): 1842-1843. doi:10.1126/science.318.5858.1842. PMID 18096770. Vogel, Gretchen ( ... or retro gaming elements, such as Minecraft and Shadow Complex. These games, which are not developed by the industry giants, ... and that she had lied about it to a grand jury investigating performance-enhancer creations. November 29, 2007 - Portsmouth ... Human genetic variation Reprogramming cells High-energy cosmic rays Receptor visions Beyond silicon: oxide interfaces Quantum ...
The protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and ... 1998). "Refined genetic mapping of the darier locus to a ... specifically to domain C of the tax-responsive enhancer element ...
Representing the genetic wealth of the Great Houses, Takisian women of childbearing years are relegated to Raranna, (the ... A masked, bow and arrow wielding vigilante, Yeoman was a deadly menace to the criminal element of New York, especially the ... The virus (known to the Takisians as "the Enhancer"), was intended to boost their own natural psionic powers, allowing his ... Sent to investigate the results of their genetic tampering with the human race, and believing Earth to be doomed by the Swarm's ...
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 ...
"Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements". Genes & ... Dean has also made a massive contribution to the development of Arabidopsis as a model, establishing resources for genetic ...
Two enhancers designated enhancer I (EnhI) and enhancer II (EnhII) have been identified in the HBV genome. Both enhancers ... Several non-coding RNA elements have been identified in the HBV genome. These include: HBV PREalpha, HBV PREbeta and HBV RNA ... Kay A, Zoulim F (August 2007). "Hepatitis B virus genetic variability and evolution". Virus Research. 127 (2): 164-76. doi: ... Antonucci TK, Rutter WJ (February 1989). "Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue- ...
"Enhancer Elements, Genetic" by people in Harvard Catalyst Profiles by year, and whether "Enhancer Elements, Genetic" was a ... Regulatory Elements, Transcriptional [G05.360.340.024.340.137.750]. *Enhancer Elements, Genetic [G05.360.340.024.340.137. ... "Enhancer Elements, Genetic" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Enhancer Elements, Genetic*Enhancer Elements, Genetic. *Element, Genetic Enhancer. *Elements, Genetic Enhancer ...
Enhancer Elements, Genetic / physiology* * Gene Deletion * Gene Expression Regulation / physiology* * Glucuronosyltransferase ... The enhancer contains 3 putative nuclear receptor motifs, and it was activated by the nuclear orphan receptor, human ... The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the ... We have now delineated the PB response activity to a 290-bp distal enhancer sequence (-3483/-3194) of the UGT1A1 gene. ...
Regulatory elements, such as enhancers, can be located in introns. Other noncoding regions are found between genes and are ... Genetic Science Learning Center, University of Utah: RNAs Role in the Central Dogma, Telomeres, and Centromeres ... Enhancers provide binding sites for proteins that help activate transcription. Enhancers can be found on the DNA strand before ... Some prevent enhancers from aiding in transcription (enhancer-blocker insulators). Others prevent structural changes in the DNA ...
The Reuven Agami Research Group develops innovative genomic and genetic tools and use them to identify cancer vulnerabilities ... Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Systematic identification of noncoding ... We identified several functional enhancer elements and characterized the role of two of them in mediating p53 (TP53) and ERα ( ... Moreover, we show that a genomic CRISPR-Cas9 tiling screen can precisely map functional domains within enhancer elements. Our ...
Our high-throughput pgRNA genome deletion method will enable rapid identification of functional mammalian non-coding elements. ... but high-throughput screening of non-coding elements using this method is more challenging because indels caused by a single ... Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat. Biotechnol. 34, 192-198 (2016). ... Gillies, S.D., Morrison, S.L., Oi, V.T. & Tonegawa, S. A tissue-specific transcription enhancer element is located in the major ...
Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nature Genetics. 45 (3): 325-329. ... The design of life: part 3-an introduction to variation-inducing genetic elements. Journal of Creation. 23 (1): 99-106. ... but also many different regulatory elements that function as key genetic switches.5 ... First, genetic data indicate that these sequences are not millions of years old. Using the comparative tools of evolutionary ...
Enhancer 59% * Epithelial Cells 36% * Genetic Promoter Regions 24% * Genetic Enhancer Elements 16% ... Vance, K. W., 24 Sep 2016, Enhancer RNAs: Methods and Protocols. Andersson Orom, U. (ed.). New York, U. S. A.: Springer, p. 39- ... A novel silencer element in the bovine papillomavirus type 4 promoter represses the transcriptional response to papillomavirus ... Novel cis-regulatory modules control expression of the Hairy and Enhancer of Split-1 (HES1) transcription factor in myoblasts. ...
... non-protein coding RNAs transcribed from enhancers. Enhancers are non-coding genetic regulatory elements that regulate cell- ... Harrison LJ & Bose D (2022) Enhancer RNAs step forward: new insights into enhancer function. Development. , 149(16). ... We look at how the unique sequence and structure of eRNAs allows them to control gene expression in enhancer-specific ways and ... Rappas M, Bose D & Zhang X (2007) Bacterial enhancer-binding proteins: unlocking σ54-dependent gene transcription. Current ...
Title: Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem ... Ronin/Hcf-1 controls a genetic program that contributes to the unimpeded growth of embryonic stem cells. ...
Genetic Enhancer Elements 17% 31 Scopus citations * Fine-mapping of the 1p11.2 breast cancer susceptibility locus. Horne, H. N ... Genetic predisposition to ductal carcinoma in situ of the breast. Petridis, C., Brook, M. N., Shah, V., Kohut, K., Gorman, P., ... Combined genetic and splicing analysis of BRCA1 c.[594-2A,C; 641A,G] highlights the relevance of naturally occurring in-frame ... Genetic risk score mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal ...
LTR enhancer element(s) (hatched rectangle), signature 21-bp repeat(s) (gray shading), and putative c-Myb binding sites (black ... Donahue PR, Quackenbush SL, Gallo MV, deNoronha CM, Overbaugh J, Hoover EA, Viral genetic determinants of T-cell killing and ... Molecular genetic characterization of the RD-114 gene family of endogenous feline retroviral sequences. J Virol. 1984;52:164-71 ... Genetic Characterization of Feline Leukemia Virus from Florida Panthers Meredith A. Brown*, Mark W. Cunningham†, Alfred L. Roca ...
... another type of genetic element known as enhancers clustered in a separate 3D compartment. Enhancers are not themselves genes ... "We previously discovered a group of enhancers, we named the Greek Islands, located near the various olfactory receptor genes," ... "These contacts are orchestrated by intergenic olfactory receptor enhancers, the Greek islands, which first contribute to the ... "This work showed that these enhancers create hotspots of activity to regulate the "chosen" olfactory receptor gene. ...
These may affect splice site sequences directly, or may disrupt regulatory elements such as exonic splicing enhancers (ESE). ... Many human genetic diseases are due to point mutations that cause aberrant splicing. ...
Genetic Enhancer Elements 9% * Clustered Regularly Interspaced Short Palindromic Repeats 8% * Reporter Genes 7% ...
... testing revealed a fine structure of positive and negative regulatory elements that modulate activity of the enhancer core. ... Genetic variation of enhancer sequences is known to influence phenotypes, but the effect of enhancer variation upon enhancer ... Enhancer polymorphisms segregate in wild A. coluzzii populations in West Africa. Thus, enhancer variants that modify target ... a typical property of enhancers. All of the enhancers segregated genetically polymorphic alleles, which displayed significantly ...
Genetic Enhancer Elements Medicine & Life Sciences 32% * Micelle Chemical Compounds 21% View full fingerprint ... Transcriptional enhancer elements are found in the 5 upstream regions of casein genes but have also been detected in the first ... Transcriptional enhancer elements are found in the 5 upstream regions of casein genes but have also been detected in the first ... Transcriptional enhancer elements are found in the 5 upstream regions of casein genes but have also been detected in the first ...
Keywords - enhancer blocking, chromatin, boundary elements Symbol - CTCF FlyBase ID: FBgn0035769 Genetic map position - 3L: ... Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene ... Insulator elements with enhancer-blocking activity curb enhancer activity, such that only appropriate promoters are activated. ... PE enhancer activates transcription in the ventral-most region where twist is normally expressed. Enhancer elements are ...
... which made parts of DNA closer together and allowed genes to be activated by regulatory elements known as enhancers. The two ... Causal Inference of Genetic Variants and Genes in Amyotrophic Lateral Sclerosis. Siyu Pan1,2, Xinxuan Liu1,3, Tianzi Liu1, ... representing the most robust genetic associations. Identifying causal genetic variants, causal genes, and cell or tissue site ... Citation: Pan S, Liu X, Liu T, Zhao Z, Dai Y, Wang Y-Y, Jia P and Liu F (2022) Causal Inference of Genetic Variants and Genes ...
Her work has highlighted the enrichment of AD risk variants in microglial enhancers, regulatory elements in DNA that control ... Goate is a leader in the study of late-onset AD genetics using integrative genomic approaches to identify novel genetic risk ... Her notable accomplishments in the field include the discovery of genetic mutations and risk factors in AD. The progress that ... Goate continued, "A fundamental understanding of the genetic basis of disease and human traits can and will lead to major ...
In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements.,h4, ... h4,Background,/h4,Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of ... Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic ...
These changes affect regions of DNA known as regulatory elements, which help turn on or turn off genes (known as enhancers or ... These genetic changes delete, insert, or rearrange genetic material near the PITX1 gene; at least five such mutations have been ... Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements. Dev Biol. 2013 Feb 1;374(1): ... Health Conditions Related to Genetic Changes. Liebenberg syndrome. Changes in the DNA near the PITX1 gene cause Liebenberg ...
... conserved regulatory elements provide a new window to the genetic and epigenetic causes of related human disease. ... Other enhancers required for somite development are likely to be located further downstream (Bolt et al., 2014). These novel, ... Kim, J., Frey, W. D., Sharma, K., Ghimire, S., Teruyama, R., & Stubbs, L. (2019). Allele-specific enhancer interaction at the ... We are exploring key TF nodes to discover their regulatory targets and to investigate how their genetic variation translates to ...
Genetic Enhancer Elements Medicine & Life Sciences 9% * Simian virus 40 Medicine & Life Sciences 9% ... The albumin enhancer was functional in some but not all albumin-positive cells. The minimal albumin enhancer was mapped to a ... The albumin enhancer was functional in some but not all albumin-positive cells. The minimal albumin enhancer was mapped to a ... The albumin enhancer was functional in some but not all albumin-positive cells. The minimal albumin enhancer was mapped to a ...
... promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases ... Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional ... Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have ... Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that ...
Genetic Enhancer Elements 10% * Ectoderm 10% * Eye 10% * Phenotype 10% * Diptera 9% ...
Genetic Enhancer Elements 100% * Gene Expression 47% * Introns 32% * Nucleotides 18% * Deoxyribonucleases 14% ... Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to ... Identification of an intronic enhancer that nullifies upstream repression of SPARC gene expression. Satyamoorthy, K., ...
The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell- ... However, translating specific genetic diagnoses into targeted genetic therapies remains a central goal. To date, genetic ... Genetic Disease and Therapy. Annual review of pathology Roth, T. L., Marson, A. 2021; 16: 145-166 Abstract. Genetic diseases ... Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that ...
eMS were enriched for regions predicted to be regulatory by ENCODE (Encyclopedia of DNA Elements) data in multiple cell types, ... Cohort studies; Health effects; Genetic factors; Genes; Gene expression; DNA; Deoxyribonucleic acids; Genomics ... in the promoter/enhancer region of the glutathione S-transferase theta 1 gene (GSTT1, encoding the detoxification enzyme) with ... particularly enhancers. One of the strongest association signals detected (P < 2.2 × 10-308) was a methylation probe ( ...
The translocation of existing enhancers, as well as enhancer loss or acquisition of insulator elements that interact with gene ... cis-regulatory elements interact which each other to control gene expression by bringing distant regulatory elements, such as ... and hormonal response as part of the mechanisms that lead to the acquisition of enhancers or super-enhancers. ... enhancers and insulators, into close proximity with promoters. It is well known that chromatin connections may be disrupted in ...
  • 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). (
  • 3,4 Not only are important genes contained in these sequences, but also many different regulatory elements that function as key genetic switches. (
  • In the African malaria vector, Anopheles coluzzii, we identified candidate enhancers in the proximity of genes relevant for immunity, insecticide resistance, and development. (
  • Transcriptional enhancer elements are found in the 5' upstream regions of casein genes but have also been detected in the first intron of the bovine beta-casein gene. (
  • proposed lists of genes with high probabilities of causality, providing a better understanding of the genetic basis of the pathogenesis of ALS. (
  • These changes affect regions of DNA known as regulatory elements, which help turn on or turn off genes (known as enhancers or repressors, respectively). (
  • The mutations that cause Liebenberg syndrome likely relocate enhancers that promote the activity of genes involved in upper limb development to be near the PITX1 gene. (
  • Within these domains, regulatory elements may interact with local promoters, regardless of gene boundaries, and confer some level of co-regulation upon the neighboring genes. (
  • The classical tool for discovering these long-range regulatory effects and for linking distant regulatory elements with gene promoters has been genome rearrangements, such as translocations and deletions, which occur far from genes but yet disrupt their tissue-specific and/or temporal expression. (
  • The Symposium Proceedings addresses 21st Century Genetics: Genes at Work, and provides a current synthesis of genetic mechanisms and genome/chromosome biology. (
  • Overexpression of SSAP in sea urchin embryos by microinjection of either synthetic mRNA or an SSAP expression vector results in four- to eightfold transactivation of target reporter genes that contain the enhancer sequence. (
  • By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. (
  • This paper demonstrated, for the first time, that toxic metal element AS induces phase II detoxification genes by activating Nrf2. (
  • What is less commonly appreciated is that there is another major class of DNA segments called "enhancers' that control the activities of genes, and arguably play an equally important role as genes. (
  • Indeed, 90% of known disease-related mutations in the human genome lie outside of genes, in regulatory sequences such as enhancers. (
  • Enhancers function by influencing the activity ("expression") of nearby genes. (
  • Genetics is the study of genes , heredity , and the variation of organisms , as well as the medical practice of diagnosing, treating, and counseling patients with genetic disorders . (
  • A multi-omics analysis revealed differentially active genes and enhancers during cortical development. (
  • We show that the transgenerational loss of fertility in piRNA mutants is not caused by de-repression of repetitive elements, as previously thought, but rather by the epigenetic silencing of all the replicative histone genes. (
  • Compatibility rules of human enhancer and promoter sequences. (
  • 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. (
  • These may affect splice site sequences directly, or may disrupt regulatory elements such as exonic splicing enhancers (ESE). (
  • Genetic variation of enhancer sequences is known to influence phenotypes, but the effect of enhancer variation upon enhancer functional activity and downstream phenotypes has barely been examined in any species. (
  • Recent work has shown that both sequence-turnover (the insertion or deletion of functional element-containing sequences) and functional-turnover (the evolutionary gain or loss of functional activity between homologous sequences) has been common in mammalian evolution. (
  • with 16 loci being identified in at least two GWASs, representing the most robust genetic associations. (
  • Dissecting the regulatory roles of polymorphic loci have been impossible without close integration of modern experimental approaches with computer analysis of a growing wealth of genetic and biological data obtained using omics technologies. (
  • Although a few loci have been associated with disease susceptibility, most of the genetic contributions to AIS await discovery. (
  • Biological insights from 108 schizophrenia-associated genetic loci. (
  • Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang ß-Thalassemia Intermedia Patients. (
  • Promoters are sites of transcription initiation that harbour a high concentration of phenotype-associated genetic variation. (
  • The presence of an evolutionary volatile promoter within a gene is associated with increased expression variance between individuals, but only in the case of human-inserted and mouse-deleted promoters does that correspond to an enrichment of promoter-proximal genetic effects. (
  • Thus, genetic variation in noncoding regions of the genome can increase the susceptibility to diseases by disrupting various regulatory elements (promoters, enhancers, silencers, insulator regions, etc. (
  • A triggering event mediating the effect of a pathogenic genetic variant on the level of gene expression can be, for example, a change in the functional activity of transcription factor binding sites (TFBSs) or DNA methylation change, which, in turn, affects the functional activity of promoters or enhancers. (
  • Research in recent decades has shown that much of the remaining noncoding genetic material holds regulatory elements - such as promoters, enhancers, silencers, and insulators - that control how the coding DNA is expressed. (
  • Like enhancers, silencers can be found before or after the gene they control and can be some distance away on the DNA strand. (
  • In addition, these intronic enhancer elements augment the induction of the beta-casein promoter by lactogenic hormones. (
  • Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor ( CNTFRalpha ) gene by the TR4 orphan receptor. (
  • Enhancers provide binding sites for proteins that help activate transcription. (
  • The EFII cis element is a 38-bp sequence at the 5' end of the Rous sarcoma virus long terminal repeat, extending from nucleotides -229 to -192 (with respect to the viral transcription start site), which is recognized by sequence-specific DNA-binding proteins in avian fibroblast nuclear extracts (L. Sealy and R. Chalkley, Mol. (
  • Sears, RC & Sealy, L 1992, ' Characterization of nuclear proteins that bind the EFII enhancer sequence in the Rous sarcoma virus long terminal repeat ', Journal of virology , vol. 66, no. 11, pp. 6338-6352. (
  • Characterization of sequence determinants of enhancer function using natural genetic variation. (
  • Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation. (
  • We are exploring key TF nodes to discover their regulatory targets and to investigate how their genetic variation translates to differences in behavioral response. (
  • In 1995, faced with the compounding ef- netic analysis of panther FeLV, designated FeLV-Pco, de- fects of reduced genetic variation, probable depression of termined that the outbreak likely came from 1 cross-spe- numbers from inbreeding, and evidence of compromised cies transmission from a domestic cat. (
  • The FeLV-Pco virus health, wildlife managers released 8 female Texas pumas was closely related to the domestic cat exogenous FeLV-A into southern Florida to increase genetic variation and ame- subgroup in lacking recombinant segments derived from liorate the physiologic effects of inbreeding. (
  • Analysis of protein-coding genetic variation in 60,706 humans. (
  • By designing and applying a pipeline to identify pathogenic genetic variation within enhancer elements responsible for regulating gene expression, we identify disease-associated variation within CAV1/CAV2 enhancers, which replicate in an independent cohort. (
  • Significant brain tissue gene expression and drug set enrichment was observed, along with shared genetic variation of SA with ADHD, smoking, and risk tolerance after conditioning on both major depressive disorder and post-traumatic stress disorder. (
  • The activity of the albumin promoter and enhancer constructs in primary hepatocytes was also measured. (
  • However, in two lines the replication defect can be rescued by the spontaneous insertion of a CMV promoter and enhancer into the U3 region. (
  • Harrison LJ & Bose D (2022) Enhancer RNAs step forward: new insights into enhancer function . (
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  • The mutation does, however, affect CP190 recruitment to specific insulator elements and has a modest effect on CTCF chromatin association. (
  • Summarizing internal dynamics boosts differential analysis and functional interpretation of super enhancers. (
  • Single cell enhancer activity distinguishes GABAergic and cholinergic lineages in embryonic mouse basal ganglia. (
  • She is now building upon these genetic insights using genome-editing in induced pluripotent stem cells to understand the molecular mechanisms underlying disease risk and protection to develop novel therapeutics. (
  • We describe ied extensively by monitoring a large proportion of adults the molecular genetic characterization of circulating FeLV by radio telemetry ( 2 - 5 ). (
  • The present review focuses on the molecular genetic mechanisms by which pathogenic genetic variants affect gene expression. (
  • We anticipate these analyses will provide a better understanding of the molecular pathogenesis of PHACE association and verify the first causative genetic variants. (
  • However, enhancers encode molecular function in a "language" different from the genetic code, and are notoriously hard to read. (
  • Enhancer polymorphisms segregate in wild A. coluzzii populations in West Africa. (
  • Association Between Genetic Polymorphisms and Hb F Levels in Heterozygous ß-Thalassemia 3.5?kb Deletions. (
  • Our high-throughput pgRNA genome deletion method will enable rapid identification of functional mammalian non-coding elements. (
  • Our research focuses on the mechanism of enhancer RNAs (eRNAs), non-protein coding RNAs transcribed from enhancers. (
  • PIWI-interacting RNAs (piRNAs) are considered to be the "guardian of the genome" given their ability to repress transposable elements and preserve genome integrity in animal germlines. (
  • Catizone AN, Uzunbas GK, Celadova P, Kuang S, Bose D & Sammons MA (2020) Locally acting transcription factors regulate p53-dependent cis-regulatory element activity . (
  • The sequence motif recognized by EFIIa, -b, and -c is also found in consensus binding sites for members of a rapidly growing family of transcription factors related to the CCAAT/enhancer-binding protein (C/EBP). (
  • However, identification of the mechanisms of influence of pathogenic genetic variants on the diseases risk is difficult due to a wide variety of regulatory elements. (
  • This enhancer element mediates the transcriptional activation of the late histone H1 gene in a temporally specific manner at the mid-blastula stage of embryogenesis. (
  • in humans, enhancers are hotspots for mutations in a number of diseases. (
  • We look at how the unique sequence and structure of eRNAs allows them to control gene expression in enhancer-specific ways and what happens when this process goes wrong, for example in diseases such as ALS where enhancers are hotspots for mutations. (
  • Many human genetic diseases are due to point mutations that cause aberrant splicing . (
  • Her notable accomplishments in the field include the discovery of genetic mutations and risk factors in AD. (
  • Unlike the mutations that cause Liebenberg syndrome (described above), these genetic changes reduce the amount of functional PITX1 protein, which disrupts normal development of the lower limbs. (
  • These tools could eventually shed new light on how genetic mutations lead to disease and could lead to new understanding of how genetic sequence influences the spatial organization and function of chromosomal DNA in the nucleus, said study author Jian Zhou, Ph.D. , Assistant Professor in the Lyda Hill Department of Bioinformatics at UTSW. (
  • By applying Sei to human genetics data, the researchers were able to characterize the regulatory architecture of 47 traits and diseases recorded in the UK Biobank database and explain how mutations in regulatory elements cause specific pathologies. (
  • three elements within this fragment recently shown to be necessary for enhancer function in a murine hepatocyte cell line were also essential for albumin enhancer function in the rat hepatocyte cell line CWSV1. (
  • Dr. Goate is a leader in the study of late-onset AD genetics using integrative genomic approaches to identify novel genetic risk factors. (
  • In modern research, genetics provides important tools in the investigation of the function of a particular gene, e.g. analysis of genetic interactions . (
  • They also identified the duplicated downstream enhancer elements termed multienhancers (ME.1 and ME.2), and demonstrated that these elements are crucial for apoE expression in macrophages and adipocytes [ 6 ]. (
  • A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma. (
  • Donahue PR , Quackenbush SL , Gallo MV , deNoronha CM , Overbaugh J , Hoover EA , Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. (
  • This volume spans a broad range of topics that reflect our current understanding of genetic mechanisms in humans and other organisms. (
  • Arsenic (AS) is a major toxic metal element and a proven carcinogen in humans. (
  • Some prevent enhancers from aiding in transcription (enhancer-blocker insulators). (
  • Some insulators can function as both an enhancer blocker and a barrier. (
  • The enhancer contains 3 putative nuclear receptor motifs, and it was activated by the nuclear orphan receptor, human constitutive active receptor (hCAR), in cotransfected HepG2 cells. (
  • Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. (
  • An integrated encyclopedia of DNA elements in the human genome. (
  • Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. (
  • Dr. Goate continued, "A fundamental understanding of the genetic basis of disease and human traits can and will lead to major changes in the way we diagnose, prevent, and treat disease across all medical specialties. (
  • During his PhD work at UCSF with Dr. Alex Marson, he developed non-viral genome targeting, a new efficient method for large scale genetic engineering of diverse primary human immune cell types without the need for complex viral vectors. (
  • A conserved hormone response element, CNTFR - DR1 (5'-AGGTCAGAGGTCAGG-3'), has been identified in the 5th intron of the alpha component of the ciliary neurotrophic factor receptor ( CNTFRalpha ) gene for the human TR4 orphan receptor (TR4). (
  • We have recently shown that replication of amphotropic MLV in specific human sarcoma and lymphoma lines is possible in the absence of the viral 75-bp transcription enhancer elements. (
  • Here, we have tested the replication of an amphotropic MLV, MLV-(MOA), and an enhancer-deficient mutant of this virus in human breast carcinoma-derived cell lines. (
  • Bone marrow cells from pAML sufferers expressing excessive ranges of IL-6 and IL-6 receptors had been cultured in human bone marrow stromal cells (HS-5 cells), which replicate the patterns of bone marrow stromal cell expression akin to secretion of IL-6, IL-1β, the ligand for receptor-type protein-tyrosine kinase (KIT), and macrophage/granulocyte colony-stimulating elements M-CSF, G-CSF, and GM-CSF. (
  • This study also indicated a potential beneficial role of repetitive elements in the human genome. (
  • Enhancers are cis-regulatory elements that control most of the developmental and spatial gene expression in eukaryotes. (
  • All of the enhancers segregated genetically polymorphic alleles, which displayed significantly different levels of functional activity. (
  • These results demonstrate the existence of naturally polymorphic A. coluzzii enhancers, which may help explain important differences between individuals or populations for malaria transmission efficiency and vector adaptation to the environment. (
  • Plank JL, Dean A. Enhancer function: mechanistic and genome-wide insights come together. (
  • The NIH Gabriella Miller Kids First Pediatric Research Program (Kids First) and the Knockout Mouse Phenotyping Program (KOMP2) are collaborating on a pilot project to develop mouse strains to study, phenotype, and validate coding and noncoding genetic variants (e.g. missense, structural variants, copy number variants, INDELS, frame shifts) identified from Kids First datasets. (
  • We have now delineated the PB response activity to a 290-bp distal enhancer sequence (-3483/-3194) of the UGT1A1 gene. (
  • The candidate enhancers were functionally validated using luciferase reporter assays, and their activity was found to be essentially independent of their physical orientation, a typical property of enhancers. (
  • Deletion mutagenesis and functional testing revealed a fine structure of positive and negative regulatory elements that modulate activity of the enhancer core. (
  • First, transcriptional enhancer elements present in the intron increase the basal activity of the beta-casein promoter. (
  • To better understand these regulatory components, he and colleagues at Princeton University and the Flatiron Institute developed a deep learning model they named Sei , which accurately sorts these snippets of noncoding DNA into 40 "sequence classes" or jobs - for example, as an enhancer for stem cell or brain cell gene activity. (
  • A reporter gene assay using chloramphenicol acetyltransferase demonstrated that the 5th intron of CNTFRalpha has an enhancer activity which could be induced by TR4 in a dose-dependent manner. (
  • Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. (
  • eMS were enriched for regions predicted to be regulatory by ENCODE (Encyclopedia of DNA Elements) data in multiple cell types, particularly enhancers. (
  • 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. (
  • Existence of HbF Enhancer Haplotypes at HBS1L-MYB Intergenic Region in Transfusion-Dependent Saudi ß-Thalassemia Patients. (
  • Enhancers can usually function in either orientation and at various distances from a promoter. (
  • 2013. Endogenous retroviruses function as species-specific enhancer elements in the placenta. (
  • Her work has highlighted the enrichment of AD risk variants in microglial enhancers, regulatory elements in DNA that control gene expression in immune cells of the brain. (
  • Phenotype and genetic heterogeneity between patients are conjectured to greatly reduce the power of overall genome-wide case-control studies in ASD, and is a likely explanation for the lack of replication and much of the 'missing heritability' in this complex disease [ 15 ]. (
  • The identity of regulatory elements and other functional regions in noncoding DNA is not completely understood. (
  • CRISPR-Cas9 screens have been widely adopted to analyze coding-gene functions, but high-throughput screening of non-coding elements using this method is more challenging because indels caused by a single cut in non-coding regions are unlikely to produce a functional knockout. (
  • Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. (
  • Lipodystrophies are categorized based on etiology (genetic or acquired) and distribution of lost adipose tissue, affecting the entire body (generalized) or only regions (partial). (
  • It is now possible to routinely associate genetic variants with phenotypes such as health outcomes or disease risk using family based or association studies. (
  • abstract = "Stage-specific activator protein (SSAP) is a 43-kDa polypeptide that binds to an enhancer element of the sea urchin late histone H1 gene. (
  • abstract = "The nuclear factor of activated T cells (NFAT) enhancer element of the IL-2 gene can regulate expression of the Escherichia coli lacZ reporter gene in activated T cells. (
  • Systematic identification of genomic elements that regulate FCGR2A expression and harbor variants linked with autoimmune disease. (
  • For this purpose, we develop innovative genomic and genetic tools and use them to identify cancer vulnerabilities. (
  • We have made substantial investments in the future of genetic and genomic research which have led to developments in diagnostics and next-generation treatments We will continue this momentum under the leadership of a dynamic and visionary scientist. (
  • Coupled enhancer and coding sequence evolution of a homeobox gene shaped leaf diversity. (
  • We show that evolution of an enhancer element in the homeobox gene REDUCED COMPLEXITY (RCO) altered leaf shape by changing gene expression from the distal leaf blade to its base. (
  • Therefore, this study helps to change the current dogma that upregulation of repetitive elements underlies the sterility in piRNA mutants. (
  • We demonstrate that multiple copies of the EFII cis element strongly activate transcription of a reporter gene in vivo. (
  • The ample use of genome-wide and exome-wide association study methodology (GWAS and EWAS) made it possible to identify a large number of genetic variants associated with diseases. (
  • This 400kb region is rich with genetic variants associated with blood cell traits such as platelet count, myeloid white cell count, and neutrophil percentage of white cells(11,12). (
  • Pooled screening of TCR and CAR T cell therapies has highlighted synthetic genetic perturbations with improved context dependent fitness profiles matched to specific solid tumor settings. (
  • Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. (
  • Whole genome and whole exome sequencing technologies play a very important role in the studies of the genetic aspects of the pathogenesis of various diseases. (