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.
Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.
Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.
Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.
Formation of an acetyl derivative. (Stedman, 25th ed)
A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.
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.
The specific patterns of changes made to HISTONES, that are involved in assembly, maintenance, and alteration of chromatin structural states (such as EUCHROMATIN and HETEROCHROMATIN). The changes are made by various HISTONE MODIFICATION PROCESSES that include ACETYLATION; METHYLATION; PHOSPHORYLATION; and UBIQUITINATION.
A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 1; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes.
Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.
Proteins involved in the assembly and disassembly of HISTONES into NUCLEOSOMES.
The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.
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)
A class of weak acids with the general formula R-CONHOH.
An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.
A family of histone demethylases that share a conserved Jumonji C domain. The enzymes function via an iron-dependent dioxygenase mechanism that couples the conversion of 2-oxoglutarate to succinate to the hydroxylation of N-methyl groups.
Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.
A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.
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.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
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.
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.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
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.
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.
Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure.
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.
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.
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).
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A multisubunit enzyme complex that regulates GENETIC TRANSCRIPTION by deacetylating the HISTONE residues of NUCLEOSOMES.
An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
Established cell cultures that have the potential to propagate indefinitely.
Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.
An enzyme that catalyzes the endonucleolytic cleavage to 3'-phosphomononucleotide and 3'-phospholigonucleotide end-products. It can cause hydrolysis of double- or single-stranded DNA or RNA. (From Enzyme Nomenclature, 1992) EC
A histone chaperone that facilitates nucleosome assembly by mediating the formation of the histone octamer and its transfer to DNA.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A cell line derived from cultured tumor cells.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
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 introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.
A retinoblastoma-binding protein that is involved in CHROMATIN REMODELING, histone deacetylation, and repression of GENETIC TRANSCRIPTION. Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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 systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.
A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.
A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.
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
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 homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.
Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.
A family of histone molecular chaperones that play roles in sperm CHROMATIN decondensation and CHROMATIN ASSEMBLY in fertilized eggs. They were originally discovered in XENOPUS egg extracts as histone-binding factors that mediate nucleosome formation in vitro.
Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.
The process by which a DNA molecule is duplicated.
A member of the p300-CBP transcription factors that was originally identified as a binding partner for ADENOVIRUS E1A PROTEINS.
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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Somewhat flattened, globular echinoderms, having thin, brittle shells of calcareous plates. They are useful models for studying FERTILIZATION and EMBRYO DEVELOPMENT.
A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692)
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
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.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A histone chaperone protein that plays a role in the deposition of NUCLEOSOMES on newly synthesized DNA. It is comprised of three different subunits of 48, 60, and 150 kDa molecular size. The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
This ribonucleoprotein particle, composed of U7 snRNA, Sm core protein, and U7 snRNP-specific proteins, is involved in the 3'end processing of histone premessenger RNAs.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
Macromolecular complexes formed from the association of defined protein subunits.
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.
Factors that are involved in directing the cleavage and POLYADENYLATION of the of MESSENGER RNA near the site of the RNA 3' POLYADENYLATION SIGNALS.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The rate dynamics in chemical or physical systems.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
A retinoblastoma-binding protein that has an affinity for core HISTONES. It is found as a subunit of protein complexes that are in involved in the enzymatic modification of histones including the Mi2 and Sin3 histone deacetylase complexes and the polycomb repressive complex 2.
A enzyme complex involved in the remodeling of NUCLEOSOMES. The complex is comprised of at least seven subunits and includes both histone deacetylase and ATPase activities.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.
A family of low-molecular weight, non-histone proteins found in chromatin.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A group of 6-alkyl SALICYLIC ACIDS that are found in ANACARDIUM and known for causing CONTACT DERMATITIS.
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.
Proteins conjugated with nucleic acids.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
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.
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.
Proteins found in any species of fungus.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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.
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 retinoblastoma binding protein that is also a member of the Jumonji-domain histone demethylases. It has demethylation activity towards specific LYSINE residues found on HISTONE H3.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
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.
A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.
A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A set of nuclear proteins in SACCHAROMYCES CEREVISIAE that are required for the transcriptional repression of the silent mating type loci. They mediate the formation of silenced CHROMATIN and repress both transcription and recombination at other loci as well. They are comprised of 4 non-homologous, interacting proteins, Sir1p, Sir2p, Sir3p, and Sir4p. Sir2p, an NAD-dependent HISTONE DEACETYLASE, is the founding member of the family of SIRTUINS.
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 steps that generate the 3' ends of mature RNA molecules. For most mRNAs (RNA, MESSENGER), 3' end processing referred to as POLYADENYLATION includes the addition of POLY A.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
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.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Proteins prepared by recombinant DNA technology.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
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.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The turning off of GENETIC TRANSCRIPTION in certain regions of CHROMATIN without changes in the DNA sequence. Typically epigenetic repression is a way that developmental changes are programmed at the cellular level.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
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.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
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).
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A multisubunit polycomb protein complex with affinity for CHROMATIN that contains methylated HISTONE H3. It contains an E3 ubiquitin ligase activity that is specific for HISTONE H2A and works in conjunction with POLYCOMB REPRESSIVE COMPLEX 2 to effect EPIGENETIC REPRESSION.
A subclass of histone deacetylases that are NAD-dependent. Several members of the SIRTUINS family are included in this subclass.
An enzyme which catalyzes the release of BIOTIN from biocytin. In human, defects in the enzyme are the cause of the organic acidemia MULTIPLE CARBOXYLASE DEFICIENCY or BIOTINIDASE DEFICIENCY.
The functional hereditary units of FUNGI.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Transcription factors whose primary function is to regulate the rate in which RNA is transcribed.
Elements of limited time intervals, contributing to particular results or situations.
Constituent of the 50S subunit of prokaryotic ribosomes containing about 120 nucleotides and 34 proteins. It is also a constituent of the 60S subunit of eukaryotic ribosomes. 5S rRNA is involved in initiation of polypeptide synthesis.
The sum of the weight of all the atoms in a molecule.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
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.
A species of ciliate protozoa used in genetic and cytological research.
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
Transport proteins that carry specific substances in the blood or across cell membranes.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.
A genus of ciliate protozoa commonly used in genetic, cytological, and other research.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from
Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.
Deoxyribonucleic acid that makes up the genetic material of fungi.

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. (1/14784)

BACKGROUND: Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. RESULTS: We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. CONCLUSIONS: We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.  (+info)

Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. (2/14784)

This report demonstrates that Gadd45, a p53-responsive stress protein, can facilitate topoisomerase relaxing and cleavage activity in the presence of core histones. A correlation between reduced expression of Gadd45 and increased resistance to topoisomerase I and topoisomerase II inhibitors in a variety of human cell lines was also found. Gadd45 could potentially mediate this effect by destabilizing histone-DNA interactions since it was found to interact directly with the four core histones. To evaluate this possibility, we investigated the effect of Gadd45 on preassembled mononucleosomes. Our data indicate that Gadd45 directly associates with mononucleosomes that have been altered by histone acetylation or UV radiation. This interaction resulted in increased DNase I accessibility on hyperacetylated mononucleosomes and substantial reduction of T4 endonuclease V accessibility to cyclobutane pyrimidine dimers on UV-irradiated mononucleosomes but not on naked DNA. Both histone acetylation and UV radiation are thought to destabilize the nucleosomal structure. Hence, these results imply that Gadd45 can recognize an altered chromatin state and modulate DNA accessibility to cellular proteins.  (+info)

Stable remodeling of tailless nucleosomes by the human SWI-SNF complex. (3/14784)

The histone N-terminal tails have been shown previously to be important for chromatin assembly, remodeling, and stability. We have tested the ability of human SWI-SNF (hSWI-SNF) to remodel nucleosomes whose tails have been cleaved through a limited trypsin digestion. We show that hSWI-SNF is able to remodel tailless mononucleosomes and nucleosomal arrays, although hSWI-SNF remodeling of tailless nucleosomes is less effective than remodeling of nucleosomes with tails. Analogous to previous observations with tailed nucleosomal templates, we show both (i) that hSWI-SNF-remodeled trypsinized mononucleosomes and arrays are stable for 30 min in the remodeled conformation after removal of ATP and (ii) that the remodeled tailless mononucleosome can be isolated on a nondenaturing acrylamide gel as a novel species. Thus, nucleosome remodeling by hSWI-SNF can occur via interactions with a tailless nucleosome core.  (+info)

Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-beta promoter. (4/14784)

Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. In this report, we show that virus infection of cells results in a dramatic hyperacetylation of histones H3 and H4 that is localized to the IFN-beta promoter. Furthermore, expressing a truncated version of IRF-3, which lacks a p300/CBP interaction domain, suppresses both histone hyperacetylation and activation of the IFN-beta gene. Thus, coactivator-mediated localized hyperacetylation of histones may play a crucial role in inducible gene expression.  (+info)

Histone octamer transfer by a chromatin-remodeling complex. (5/14784)

RSC, an abundant, essential chromatin-remodeling complex related to SWI/SNF complex, catalyzes the transfer of a histone octamer from a nucleosome core particle to naked DNA. The newly formed octamer-DNA complex is identical with a nucleosome in all respects. The reaction requires ATP and involves an activated RSC-nucleosome intermediate. The mechanism may entail formation of a duplex displacement loop on the nucleosome, facilitating the entry of exogeneous DNA and the release of the endogenous molecule.  (+info)

Basic homopolyamino acids, histones and protamines are potent antagonists of angiogenin binding to ribonuclease inhibitor. (6/14784)

A radio-ribonuclease inhibitor assay based on the interaction of 125I-angiogenin with ribonuclease inhibitor (RI) was used to detect pancreatic-type ribonucleases and potential modulators of their action. We show that highly basic proteins including the homopolypeptides poly-arginine, poly-lysine and poly-ornithine, core histones, spermatid-specific S1 protein and the protamines HP3 and Z3 were strong inhibitors of angiogenin binding to RI. A minimum size of poly-arginine and poly-lysine was required for efficient inhibition. The inhibition likely resulted from direct association of the basic proteins with the acidic inhibitor, as RI bound to poly-lysine and protamines while 125I-angiogenin did not. Antagonists of the angiogenin-RI interaction are potential regulators of either angiogenin-triggered angiogenesis and/or intracellular RI function, depending on their preferential target.  (+info)

H5 Histone and DNA-relaxing enzyme of chicken erythrocytes. Interaction with superhelical DNA. (7/14784)

The interaction of closed circular duplex DNA with the lysine-rich H5 histone fraction of avian erythrocytes has been studied. H5, like H1 histone, interacts preferentially with superhelical DNA. The extent of interaction increases with increasing negative or positive superhelicity. Salt-extracted lysine-rich histones show the same specificity for interaction with superhelices as do acid-extracted preparations. Chicken erythrocyte nuclei contain DNA-relaxing enzyme. This enzyme is extracted from the nuclei at lower salt concentrations than those required to extract H1 and H5 histones and is, therefore, probably a function of a protein distinct from H1 and H5 histones.  (+info)

Proteinuria induces tubular cell turnover: A potential mechanism for tubular atrophy. (8/14784)

BACKGROUND: Proteinuria and tubular atrophy have both been closely linked with progressive renal failure. We hypothesized that apoptosis may be induced by tubular cell exposure to heavy proteinuria, potentially leading to tubular atrophy. Apoptosis was studied in a rat model of "pure" proteinuria, which does not induce renal impairment, namely protein-overload proteinuria. METHODS: Adult female Lewis rats underwent intraperitoneal injection of 2 g of bovine serum albumin (BSA, N = 16) or sham saline injections (controls, N = 8) daily for seven days. Apoptosis was assessed at day 7 in tissue sections using in situ end labeling (ISEL) and electron microscopy. ISEL-positive nuclei (apoptotic particles) were counted in blinded fashion using image analysis with NIH Image. Cell proliferation was assessed by detection of mRNA for histone by in situ hybridization, followed by counting of positive cells using NIH Image. RESULTS: Animals injected with saline showed very low levels of apoptosis on image analysis. BSA-injected rats had heavy proteinuria and showed both cortical and medullary apoptosis on ISEL. This was predominantly seen in the tubules and, to a lesser extent, in the interstitial compartment. Overall, the animals injected with BSA showed a significant 30-fold increase in the number of cortical apoptotic particles. Electron microscopy of tubular cells in a BSA-injected animal showed a progression of ultrastructural changes consistent with tubular cell apoptosis. The BSA-injected animals also displayed a significant increase in proximal tubular cell proliferation. This increased proliferation was less marked than the degree of apoptosis. CONCLUSION: Protein-overload proteinuria in rats induces tubular cell apoptosis. This effect is only partially balanced by proliferation and potentially provides a direct mechanism whereby heavy proteinuria can induce tubular atrophy and progressive renal failure.  (+info)

The activity of a single gene is influenced by the composition of the chromatin in which it is embedded. Nucleosome turnover, conformational dynamics, and covalent histone modifications each induce changes in the structure of chromatin and its affinity for regulatory proteins. The dynamics of histone modifications and the persistence of modification patterns for long periods are still largely unknown. In this study, we present a stochastic mathematical model that describes the molecular mechanisms of histone modification pattern formation along a single gene, with non-phenomenological, physical parameters. We find that diffusion and recruitment properties of histone modifying enzymes together with chromatin connectivity allow for a rich repertoire of stochastic histone modification dynamics and pattern formation. We demonstrate that histone modification patterns at a single gene can be established or removed within a few minutes through diffusion and weak recruitment mechanisms of histone modification
ALATZAS, ANASTASIOS; SREBREVA, LJUBA and FOUNDOULI, ATHINA. Distribution of linker histone variants during plant cell differentiation in the developmental zones of the maize root, dedifferentiation in callus culture after auxin treatment. Biol. Res. [online]. 2008, vol.41, n.2, pp.205-215. ISSN 0716-9760. Although several linker histone variants have been studied in both animal and plant organisms, little is known about their distribution during processes that involve alterations in chromatin function, such as differentiation, dedifferentiation and hormone treatment. In this study, we identified linker histone variants by using specific anti-histone Hl antibodies. Each variants ratio to total Hl in the three developmental zones of maize (Zea mays L.) root and in callus cultures derived from them was estimated in order to define possible alterations either during plant cell differentiation or during their dedifferentiation. We also evaluated ...
Background: Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Methods: Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. Results: By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular ...
Re histone modification profiles, which only take place inside the minority in the studied cells, but with the improved Daprodustat sensitivity of reshearing
Re histone modification profiles, which only occur inside the minority from the studied cells, but together with the increased sensitivity of reshearing these
Histones are the major protein component of nucleosomes, and de novo histone synthesis is essential for packaging newly replicated DNA into chromatin. As a result, histone gene expression is exquisitely and functionally coupled with DNA replication. Vastly divergent organisms such as yeast, fly and human all demonstrate the phylogenetically conserved propensity to maintain clustering of histone genes at one or more genomic loci. Although specific mechanisms are unclear, clustering is presumed to be important for common stringent transcriptional control of these genes at the G1/S phase transition. In this study, we describe a genomic duplication of the human histone gene cluster located at chromosome 1q21, which effectively doubles the previously known size and gene number of that cluster. The duplication persists in all examined tissues and cell lines, and the duplicated genes are transcriptionally active. Levels of messenger RNAs for duplicated histone H4 genes are high relative to those for non
This EMBO Workshop features histone variants, which are part of an interconnected epigenetic network including DNA methylation, posttranslational histone modifications, chromatin remodeling, regulatory RNAs and nuclear organization. Worldwide research on histone variants over the last years has revealed their important function in gene regulation, cell cycle progression, DNA damage repair, genome stability, cell differentiation and organism development. Additionally, recent studies have highlighted the role of mutations or deregulation of expression of histone variants and their binding partners in diverse diseases, most notably cancer.. This EMBO Workshop will provide a comprehensive representation of all of these histone variant-related processes, with a balanced portrayal of different model organisms, including rare variants in parasites and evolutionary aspects, as well as presentations of the different variant families, such as linker histone variants. Specialists of variant deposition ...
After publication of our recent article [1], it has been brought to our attention that the incorrect wording was used to acknowledge our EU funding source. The correct statement should read:. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 261382. ...
In contrast to many other genes containing a CpG island, the testis-specific H2B (TH2B) histone gene exhibits tissue-specific methylation patterns in correlation with gene activity. Characterization of the methylation patterns within a 20-kb segment containing the TH2A and TH2B genes in comparison with that in a somatic histone cluster revealed that: (i) the germ cell-specific unmethylated domain of the TH2A and TH2B genes is defined as a small region surrounding the CpG islands of the TH2A and TH2B genes and (ii) somatic histone genes are unmethylated in both liver and germ cells, like other genes containing CpG islands, whereas flanking sequences are methylated. Transfection of in vitro-methylated TH2B, somatic H2B, and mouse metallothionein I constructs into F9 embryonal carcinoma cells revealed that the CpG islands of the TH2A and TH2B genes were demethylated like those of the somatic H2A and H2B genes and the metallothionein I gene. The demethylation of those CpG islands became ...
Variability in the quality of antibodies to histone post-translational modifications (PTMs) is a widely recognized hindrance in epigenetics research. Here, we produced recombinant antibodies to the trimethylated lysine residues of histone H3 with high specificity and affinity and no lot-to-lot varia …
Both DNA methylation and post-translational histone modifications contribute to gene silencing, but the mechanistic relationship between these epigenetic marks is unclear. Mutations in two Arabidopsis genes, the KRYPTONITE (KYP) histone H3 lysine 9 (H3K9) methyltransferase and the CHROMOMETHYLASE3 (CMT3) DNA methyltransferase, cause a reduction of CNG DNA methylation, suggesting that H3K9 methylation controls CNG DNA methylation. Here we show that the chromodomain of CMT3 can directly interact with the N-terminal tail of histone H3, but only when it is simultaneously methylated at both the H3K9 and H3K27 positions. Furthermore, using chromatin immunoprecipitation analysis and immunohistolocalization experiments, we found that H3K27 methylation colocalizes with H3K9 methylation at CMT3-controlled loci. The H3K27 methylation present at heterochromatin was not affected by mutations in KYP or in several Arabidopsis PcG related genes including the Enhancer of Zeste homologs, suggesting that a novel pathway
Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication andDNA damage repair1 . The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2Ain yeast or inhibition of CK2 activityimpairs transcriptional elongation in yeast as well asin mammalian cells. Genome-wide binding analysis reveals that CK2a, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers.Mutation of Tyr 57 causes a loss of H2Bmono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks ...
Circadian clocks are biochemical mechanisms that allow eukaryotic and some prokaryotic organisms to coordinate their physiology with daily environmental changes. It enables organisms to increase their fitness by taking advantage of beneficial environmental conditions while also avoiding or restricting certain sensitive processes during harsh conditions. Similarly, post-translational histone modifications allow eukaryotic organisms to regulate gene expression in response to environmental or developmental factors. Some post-translational modifications of histones are associated with active transcription while others are associated with repressed transcription depending upon the location, type and degree of modification. Trimethylation of lysine 4 on the N-terminal tail of histone H3 (H3K4me3) near a genes promoter has been linked to active transcription of that gene in several organisms. The purpose of the current study was to investigate whether the amount of H3K4me3 at promoters of three specific genes
Purpose: Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released from dying cell and extracellular histones cause cellular damage and organ dysfunction during sepsis, sterile inflammatory liver injury, and acute kidney injury. Regardless of these clinical significances, its role and relevance to ocular diseases have been mostly unknown. The purpose of this study was to investigate the role of histone on retinal cells and their pathology focusing on retinal detachment (RD).. Methods: The oxidative stress was introduced with H2O2 in cultured rat retinal progenitor cells R28 and the expression of histone H3 was evaluated by Western blot. RD model was produced by subretinal injection of hyaluronan in rats and the expression of H3 was examined by immunohistochemistry. In addition, we assessed the vitreous concentrations of histone H3 by enzyme-linked immune-sorbent assay and their relationships with cytokine levels a using ...
It is becoming increasingly evident that the cellular response towards DNA damage is affected by the structure of the chromatin region surrounding the damage site [1], while at the same time the chromatin structure is affected by the damage response [2]. DNA double-strand breaks (DSBs) elicit a response in an Mbp-large chromatin region surrounding the break that involves alterations in several post-translational modifications (PTMs). Phosphorylation of histone variant H2AX at serine 139 (S139) to yield γ-H2AX is a hallmark step in the cellular response to DSB. The γ-H2AX chromatin domains, which can be visualized as ionizing radiation induced foci (IRIF), delineate regions where a large variety of signalling and repair proteins accumulate [3].. Immunofluorescence detection of PTMs demonstrated alterations in several modifications in the γ-H2AX domain following DSB induction that are associated with regulation of chromatin accessibility, recruitment of DNA damage response factors, and ...
The identification of demethylase enzymes has revealed that histone methylation can be dynamically regulated in a manner similar to that of histone acetylation and phosphorylation. In S. cerevisiae, the enzymes that place histone methylation marks are well characterized and coordinate mainly the addition of these modifications during the process of active transcription (25). Previously, only one histone demethylase enzyme, Jhd1, was identified in budding yeast. Jhd1 is a JmjC-domain-containing protein that catalyzes the demethylation of H3K36me2 and H3K36me1 modification states (36). Given that Jhd1 does not target H3K36me3 in yeast, it remained possible that this methylation state was irreversible.. Here, we identify Rph1 as being a histone demethylase with activity towards histone H3K36me3 and H3K36me2 modification states. Deletion of RPH1 does not affect global histone H3K36 methylation profiles, and deletion strains are viable, displaying no obvious morphological or cellular defects. This ...
Histone N-terminal tails are extensively modified by a plethora of post-translational modifications, including histone methylation. Histone methylation has been implicated in multiple biological processes including heterochromatin formation, Xinactivation, genomic imprinting and silencing of homeotic genes. Methylation occurs on both lysine (K) and arginine (R) residues. Multiple K residues on the tails of histone H3 and H4 have been shown to be sites for methylation (mono-, di, and tri-methylation). Methylation at these sites has been linked to transcriptional activation and repression, as well as DNA damage response, indicating a widespread role for histone methylation in various aspects of chromatin biology. Unlike other histone modifications such as acetylation, methylation has long been considered a permanent modification. Our identification of the first histone demethylase LSD1 disproved this dogma, and suggested that histone methylation is dynamically regulated by both histone ...
The main goal of this project is to develop a simple, yet powerful and versatile technology for detection and imaging of epigenetic histone modifications and hi...
Aberrant gene expression is a common feature of cancer cells, which is caused by a combination of gene mutations and aberrant regulation of gene expression by epigenetic mechanisms, including DNA methylation, microRNAs and histone modifications. Histone modifications play a crucial role in many cellular processes during embryonic development, cell proliferation and cellular differentiation [2]. In cancer, aberrant expression of histone modifications has been described frequently [1]. Therefore, we investigated the nuclear expression of three well-studied histone modifications in colon cancer.. In this study, we found that nuclear expression of histone trimethylation on H3K4, H3K9 and H4K20 has prognostic value in early-stage colon cancer. Changes in expression of key histone modifications are found in early-stage tumors, which would be expected because tumor cells require instant changes in gene expression and chromatin structure in order to promote cell proliferation and tumor cell survival. ...
The field of cancer epigenetics has received much attention in recent years. However, the relationship of cancer epigenetics with cancer etiology is not clear. Recent studies suggest the involvement of altered DNA methylation and histone modifications in the emergence of epigenetically reprogrammed cells with specific tumor-related phenotypes at premalignant stages of tumor development. In this study, we used a methyl-deficient model of rodent hepatocarcinogenesis to examine the roles of DNA, histone H3 lysine 9 and histone H4 lysine 20 methylation, and the level of the expression of Suv39h1 and Suv4-20h2 histone methyltransferases in the carcinogenic process. We demonstrated that the development of liver tumors was characterized by progressive demethylation of DNA repeats, decrease in histone H4 lysine 20 trimethylation, and a gradual decrease in the expression of Suv4-20h2 histone methyltransferase. A prominent increase in the trimethylation of histone H3 lysine 9 and in the expression of ...
Introduction Hepatic steatosis is a major risk factor for the development of severe liver damage, including fibrosis, cirrhosis and hepatocellular carcinoma. It often exists as a co-morbidity factor with diabetes type I/II and with other manifestations of the metabolic syndrome. Recent studies highlight the importance of an epigenetic basis for the development of steatosis based on macroH2A1. MacroH2A1 is a histone variant of histone H2A, which possesses an additional protein domain called macro. When incorporated into the chromatin of hepatocytes, macroH2A1 regulates gene expression. Two alternatively spliced isoforms of macroH2A1 exist, which have been shown to be markers of breast, skin and lung cancer. Whole-body knock out of macroH2A1 in mice induces glucose intolerance and changes in genes regulating hepatic lipid metabolism. However, overt hepatic steatosis was not observed and the significance of these findings is unclear. We hypothesised that macroH2A1 could be involved in the ...
Histone variants play further important roles in DNA packaging and controlling gene expression. However, our understanding about their composition and their functions is limited. Integrating proteomic and genomic approaches, we performed a comprehensive analysis of the epigenetic landscapes containing the four histone variants H3.1, H3.3, H2A.Z, and macroH2A. These histones were FLAG-tagged in HeLa cells and purified using chromatin immunoprecipitation (ChIP). By adopting ChIP followed by mass spectrometry (ChIP-MS), we quantified histone post-translational modifications (PTMs) and histone variant nucleosomal ratios in highly purified mononucleosomes. Subsequent ChIP followed by next-generation sequencing (ChIP-seq) was used to map the genome-wide localization of the analyzed histone variants and define their chromatin domains. Finally, we included in our study large datasets contained in the ENCODE database. We newly identified a group of regulatory regions enriched in H3.1 and the histone variant
Mirabegron Figure S7: NUP98 associates with distinct subsets of active and silent genes in embryonic stem cells. (A) Pearsons correlation between pairs of histone modifications for NUP98 binding regions in ESCs. Histone modification levels were calculated from (Lister et al. 2011), type:entrez-geo,attrs:text:GSM605321″,term_id:605321″GSM605321, and Mirabegron type:entrez-geo,attrs:text:GSM605309″,term_id:605309″GSM605309. (B, C, and D) For each histone modification type, NUP98 binding genes were ranked by their histone modification levels and top 40% genes were selected for gene ontology analysis. Biological process categories that are uniquely enriched for specific histone modification types were shown in red for active histone marks and in blue for silent histone mark. (E, F, G, and H) Expression levels of NUP98 binding genes that were high in each of the four histone modifications were compared to those of same number of randomly selected genes. P values were ...
We describe the chromosomal location of GC-rich regions, 28S and 5S rDNA, core histone genes, and telomeric sequences in the veneroid bivalve species Venerupis aurea and Tapes (Venerupis) rhomboides,
Changes in chromatin structure play a large role in the regulation of transcription in eukaryotes (1). The nucleosome is the primary building block of chromatin, and is made up of four core histone proteins (H2A, H2B, H3 and H4) (2). Acetylation of core histones regulates gene expression (2). Histone H3 is primarily acetylated at lysines 9, 14, 18, and 23 (3,4). Acetylation at lysine 9 appears to have a dominant role in histone deposition and chromatin assembly in some organisms (3,4). Phosphorylation at Ser10 of histone H3 is tightly correlated with chromosome condensation during both mitosis and meiosis (5 ...
Tight regulation of histone relative stoichiometry and overall levels is fundamental to the preservation of genome integrity in all eukaryotes. Abnormal histone levels induce defects in mitotic chromosome segregation, chromatin structure, and transcription and lead to loss of viability (Meeks-Wagner and Hartwell 1986; Han et al. 1987; Clark-Adams et al. 1988; Kim et al. 1988; Norris et al. 1988). Defects in chromatin structure caused by inactivation of nucleosome assembly factors cause high rates of chromosomal rearrangements and spontaneous DNA damage and elicit checkpoint activation (Myung et al. 2003; Ye et al. 2003; Ramey et al. 2004).. This study provides genetic and biochemical evidence that Trf4 and Trf5 make a redundant contribution to genome stability in yeast through control of histone mRNA levels during S phase. We show that the mRNAs coding for the four core histones, but not other cell cycle-regulated transcripts tested, accumulate to abnormally high levels in S phase in a trf4-ts ...
Background Histone variants establish structural and functional diversity of chromatin by affecting nucleosome stability and histone-protein interactions. H3.3 is an H3 histone variant that is incorporated into chromatin outside of S-phase in various eukaryotes. In animals, H3.3 is associated with active transcription and possibly maintenance of transcriptional memory. Plant H3 variants, which evolved independently of their animal counterparts, are much less well understood. Results We profile the H3.3 distribution in Arabidopsis at mono-nucleosomal resolution using native chromatin immunoprecipitation. This results in the precise mapping of H3.3-containing nucleosomes, which are not only enriched in gene bodies as previously reported, but also at a subset of promoter regions and downstream of the 3′ ends of active genes. While H3.3 presence within transcribed regions is strongly associated with transcriptional activity, H3.3 at promoters is often independent of transcription. In particular, ...
Histone binding pocket. (A) Potential histone peptide binding site. Superposition of the Smyd3 and SET7/9 (PDB code 1O9S) structures was performed as in Figure
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H1 family. [provided by RefSeq, Oct 2015 ...
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. H2AFX encodes a replication-independent histone that is a member of the histone H2A family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif.
Trimethylation of histone H3 lysine 4 (H3K4me3) accumulates at promoters in a gene activity-dependent manner. The Set1 complex is responsible for most H3K4me3 in somatic cells and contains the conserved subunit Cfp1, which is implicated in targeting the Set1 complex to CpG islands in mammals. In mouse embryonic stem cells, Cfp1 is necessary for H3K4me3 accumulation at constitutively active gene promoters, but is not required to maintain steady-state transcription of the associated gene. Here we show that Cfp1 is instrumental for targeting H3K4me3 to promoters upon rapid transcriptional induction in response to external stimuli. Surprisingly, H3K4me3 accumulation is not required to ensure appropriate transcriptional output but rather plays gene-specific roles. We also show that Cfp1-dependent H3K4me3 deposition contributes to H3K9 acetylation genome-wide, suggesting that Cfp1-dependent H3K4me3 regulates overall H3K9 acetylation dynamics and is necessary for histone acetyl transferase recruitment. Finally
TY - JOUR. T1 - Systems level analysis of Histone H3 posttranslational modifications (PTMs) reveals features of PTM crosstalk in chromatin regulation. AU - Schwämmle, Veit. AU - Sidoli, Simone. AU - Ruminowicz, Chrystian. AU - Wu, Xudong. AU - Lee, Chung Fan. AU - Helin, Kristian. AU - Jensen, Ole N.. PY - 2016/8. Y1 - 2016/8. N2 - Histones are abundant chromatin constituents carrying numerous post-translational modifications (PTMs). Such PTMs mediate a variety of biological functions, including recruitment of enzymatic readers, writers and erasers that modulate DNA replication, transcription and repair. Individual histone molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk. Using wild type and engineered mouse embryonic stem cells (mESCs) knocked out in components of the Polycomb ...
The analysis of the recently available ChIP-seq data on 8 histone modification marks and 13 TF binding sites in mES cells confirmed the distinct chromatin signatures associated with promoters and enhancers. We did not observe any significant correlation between the histone modification patterns and the binding of the 13 TFs probably because none of these factors are involved in chromatin modification. The unexpected correlations between several histone marks and the binding strength of TFs (Table S3 in Additional file 2) still needs further validation and determination of the underlying molecular mechanisms.. Histone modifications reflect the epigenetic state of a cell, which provides useful information to map the functional activities of regulatory elements. In this study, we present a new computational model called Chromia that integrates sequence motif and chromatin signatures to predict target loci of TFs. We have demonstrated that the performance of our method is superior to many other ...
Post-translational histone modifications play important roles in chromatin functions, ranging from DNA damage and repair, DNA recombination, chromatin structure...
Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. The protein has antibacterial and antifungal antimicrobial activity. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015 ...
Histone modifications play important roles in chromatin remodeling, gene transcriptional regulation, stem cell maintenance and differentiation. Alterations in histone modifications may be linked to human diseases especially cancer. Histone modifications including methylation, acetylation and ubiquit …
Packaging DNA into chromatin is dynamic, reversible, and essential for eukaryotic cell viability. The principal packaging unit of chromatin is the nucleosome, consisting of an octamer of two copies each of the four canonical histones (H2A, H2B, H3, and H4) wrapped in 146 bp of DNA (1). Histone proteins are decorated with posttranslational modifications, including lysine acetylation, which influence chromatin architecture by altering nucleosome contacts or by affecting interactions with nonhistone proteins (2). During DNA-dependent processes, nucleosomes disassemble to grant access to specific regions of DNA and reassemble in a way that preserves the local chromatin landscape. By virtue of their highly basic charge, histones are prone to both aggregation and promiscuous interactions when they are not associated with DNA, such as when they are newly synthesized or during nucleosome turnover. To prevent these deleterious effects, a network of histone chaperones regulates each step of chromatin ...
Histone acetyltransferases serve many biological roles inside the cell. Chromatin is a combination of proteins and DNA found in the nucleus, and it undergoes many structural changes as different cellular events such as DNA replication, DNA repair, and transcription occur.[22] Chromatin in the cell can be found in two states: condensed and uncondensed. The latter, known as euchromatin, is transcriptionally active, whereas the former, known as heterochromatin, is transcriptionally inactive.[22][23] Histones comprise the protein portion of chromatin. There are five different histone proteins: H1, H2A, H2B, H3, and H4. A core histone is formed when two of each histone subtype, excluding H1, form a quaternary complex. This octameric complex, in association with the 147 base pairs of DNA coiled around it, forms the nucleosome.[3] Histone H1 locks the nucleosome complex together, and it is the last protein to bind in the complex.. Histones tend to be positively charged proteins with N-terminal tails ...
Recombinant Histone H3K36me3 (MLA) protein, methylated lysine analog for analysis of transcription regulation, DNA repair, DNA replication and chromosomal stability
Histones are modified at specific positions on their conserved amino‐terminal tails, and these modifications play central roles in gene regulation (Jenuwein and Allis, 2001; Turner, 2002). For example, acetylation at lysine 14 of histone H3 (H3K14Ac) or methylation of lysine 4 (H3K4Me) is associated with gene activation. In contrast, the lack of acetylation as well as the methylation of lysine 9 of histone H3 (H3K9Me) is correlated with gene repression (Jenuwein and Allis, 2001; Turner, 2002). These two types of modifications are performed by histone acetyltransferases (HATs) and histone methyltransferases (HMTases). These modifying enzymes are members of large multiprotein complexes with other subunits likely serving roles in targeting or regulation. The primary substrates for these enzymes are the amino‐terminal tails of the histone proteins. Modified tails function as binding platforms for transcriptional regulatory factors. For example, the histone H3 tail methylated at lysine 9 is ...
Histone peptide arrays are essential screening tools to evaluate the specificity and cross-reactivity of antibodies against histones H2A, H2B, H3, H4, and their post-translational modifications.The arrays are designed on PVDF membranes for a simple Western blot-like assay.
HIV-1 latency is maintained by several mechanisms. a , Transcription factors (TFs), including nuclear factor-κB (NF-κB) and nuclear factor of activated T cells (NFAT), are sequestered in the cytoplasm, which leads to transcriptional silencing. Bryostatin and prostratin induce activation of NF-κB, leading to its translocation to the nucleus where it activates HIV-1 transcription. b , The HIV-1 long terminal repeat (LTR) is flanked by the Nuc-0 and Nuc-1 nucleosomes that, when latent, can encode repressive post-translational histone modifications. Histone deacetylases (HDACs), which are recruited by transcription factors (such as YY1 and CBF-1), remove the acetyl groups from chromatin. Histone methyltransferases (HMTs), such as SUV39H1, G9a and EZH2, deposit methyl groups onto histones. HDACs and HMTs enforce the repressive state. Both HDAC inhibitors and HMT inhibitors can induce transcription from quiescent LTR promoters. HIV-1 DNA can also be methylated, although recent evidence suggests ...
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan (S.I., H.K., R.K.); Phamacokinetics Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan (S.I.); and Sugiyama Laboratory, RIKEN Innovation Center, Research Cluster for Innovation, Riken, Kanagawa, Japan (Y.S ...
The usage of ,100 functional murine Ig heavy chain V(H) genes, when rearranged to D(H)J(H) genes, generates a diverse antibody repertoire. The V(H) locus encompasses 2.5 Mb, and rearrangement of V(H) genes in the D(H)-distal half of the locus are controlled very differently from the V(H) genes in the proximal end of the locus. The rearrangement of distal but not proximal V(H) genes is impaired in mice deficient in the cytokine IL-7 or its receptor, in the transcription factor Pax5, or in Ezh2, a histone methyltransferase for Lys-27 of histone H3 (H3K27). The relative role of IL-7, Pax5, and Ezh2 in regulating distal vs. proximal V(H) rearrangement is not clear. Here, we show by ChIP and ChIP-on-chip that the active histone modification H3K36me2 is most highly associated with distal V(H) segments and the repressive histone modification H3K27me3 is exclusively present on proximal V(H) segments. We observed an absence of H3K27me3 in fetal pro-B cells, which predominantly rearrange proximal V(H) ...
Author Summary Eukaryotic DNA is packaged into chromatin through its association with histone proteins. The linker histone H1 sits at the base of the nucleosome near the DNA entry and exit sites to stabilize two full turns of DNA. In particular, histone H1 participates in nucleosome spacing and formation of the higher-order chromatin structure. In addition, H1 seems to be actively involved in the regulation of gene expression. Histone H1 in mammals is a family of closely related, single-gene encoded proteins, including five somatic subtypes (from H1.1 to H1.5) and a terminally differentiated expressed isoform (H1.0). It is not well known whether the different variants have distinct roles or if they regulate specific promoters. We have explored this by inducible knock-down of each of the H1 variants in breast cancer cells. A different subset of genes is altered in each H1 knock-down, and depletion has different effects on cell survival. Interestingly, H1.2 and H1.4 depletion specifically caused arrest of
Role of H1 Linker Histones and Chromatin Remodeling Factors in Chromatin Structure, DNA Methylation, the Histone Code, Gene Expression and Development in Mice and Drosophila. Recent studies show that posttranslational modifications of core histones (H2A, H2B, H3, H4) (the Histone Code) play a very important role in control of gene expression. The H1 linker histones are more diverse than the core histones. Mice contain 8 H1 histone subtypes including differentiation-specific and tissue-specific subtypes, whereas Drosophila has only one type of H1. H1s are thought to be responsible for the final level of packaging DNA into the compact chromatin structure but we know very little about their role in gene expression and development. We are studying the functional roles of H1 linker histones by inactivating (knocking-out) specific H1 genes in mice and the single H1 in Drosophila. We are also reintroducing mutant H1 linker histones into H1 depleted mouse cells and flies, to perform structure-function ...
Core and linker histone gene clusters have been mapped to chromosomes of two species of Mytilidae, M. galloprovincialis [26, 27] and X. securis [33]. FISH mapping of core histone gene clusters has also been performed in another three related mytilids, B. puniceus, B. rodriguezi [30] and P. purpuratus [32]. The detection of separated core and linker histone gene clusters on four chromosome pairs in Mytilus coincides with the situation in X. securis [33] and fits the molecular findings of Drabent et al. [24] and Albig et al. [25] showing separated linker and core histone gene repeats in M. edulis but partially disagrees with FISH mapping data of M. galloprovincialis [26, 27]. In this species linker histone gene clusters were assigned to three unidentified chromosome pairs [26] and core histone gene clusters to two [27]; the latter were supposed to be coincident with two of the three linker histone gene clusters [27]. The discrepancy of these FISH mapping data with our results showing separate ...
TY - JOUR. T1 - Role for a YY1-binding element in replication-dependent mouse histone gene expression. AU - Eliassen, Katherine A.. AU - Baldwin, Amy. AU - Sikorski, Eric M.. AU - Hurt, Myra M.. PY - 1998/12. Y1 - 1998/12. N2 - Expression of the highly conserved replication-dependent historic gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated α, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 α element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 α sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription ...
TY - JOUR. T1 - Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma. T2 - Results from RTOG 9704. AU - Manuyakorn, Ananya. AU - Paulus, Rebecca. AU - Farrell, James. AU - Dawson, Nicole A.. AU - Tze, Sheila. AU - Cheung-Lau, Gardenia. AU - Hines, Oscar Joe. AU - Reber, Howard. AU - Seligson, David B.. AU - Horvath, Steve. AU - Kurdistani, Siavash K.. AU - Guha, Chandhan. AU - Dawson, David W.. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2010/3/10. Y1 - 2010/3/10. N2 - Purpose: Differences in cellular levels of histone modifications have predicted clinical outcome in certain cancers. Here, we studied the prognostic and predictive value of three histone modifications in pancreatic adenocarcinoma. Methods: Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were examined, including those from a 195-patient cohort from Radiation Therapy Oncology Group trial RTOG 9704, a multicenter, ...
Covalent modification of histone tails is a major epigenetic mechanism. Furthermore, multiple intra-nucleosomal or inter-nucleosomal histone modifications are frequently observed within the same genomic loci. The histone code hypothesis postulates that multiple histone modifications act in a combinatorial fashion to specify distinct chromatin states, which in turn regulate gene activities [1, 2]. To completely characterize the histone code is a major goal of epigenetics research.. To date, Chromatin Immunoprecipitation coupled with microarray chip (ChIP-Chip) or deep sequencing (ChIP-Seq) is the predominant experimental technology for obtaining genome-wide maps of histone modifications. However, ChIP-based technologies have inherent resolution limit given the fragmentation limit of chromatin DNA [3]. Recently, mass spectrometry (MS) has been applied to effectively characterize and quantitate combinatorial histone codes within the same histone tail [4]. Generally speaking, the MS-based approach ...
Histone modifications play critical roles in regulating both global and stage-specific gene expression. Methylation on histones H3K4, H3K36 and H3K79 is generally associated with gene activation, whereas methylation on histones H3K9 and H3K27 is generally associated with gene repression. Histone lysine methylation is dynamically regulated by site-specific methyltransferases and demethylases. EZH2 (the catalytic subunit of PRC2) is responsible for the methylation of H3K27 in cells.. DOT1L is a histone H3 lysine 79 methyltransferase whose inhibition increases the yield of induced pluripotent stem cells (iPSCs). EPZ-5676 is a potent and selective DOT1L inhibitor.. Crucial to PRC2 activity, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) tri-methylates lysine 27 of histone 3 (H3K27me3), leading to chromatin condensation and transcriptional repression.. ...
Memory consolidation requires a timely controlled interplay between the hippocampus, a brain region important for memory formation, and the cortex, a region recruited for memory storage. Here we show that memory consolidation is associated with specific epigenetic modifications on histone proteins that have a distinct dynamic in these brain areas. While in the hippocampus, histone post-translational modifications (PTMs) are rapidly and transiently activated after learning, in the cortex they are induced with delay but persist over time. When these histone PTMs are increased in vivo by transgenic intervention or intense training, they facilitate memory consolidation. Conversely, when they are pharmacologically blocked, memory consolidation is impaired. These histone PTMs are further associated with the expression of the immediate early gene zif268, a transcription factor that favours memory consolidation. These findings reveal the spatiotemporal dynamics of histone marks during memory ...
TY - JOUR. T1 - The chromatin remodeling complex NuRD establishes the poised state of rRNA genes characterized by bivalent histone modifications and altered nucleosome positions. AU - Xie, Wenbing. AU - Ling, Te. AU - Zhou, Yonggang. AU - Feng, Weijun. AU - Zhu, Qiaoyun. AU - Stunnenberg, Henk G.. AU - Grummt, Ingrid. AU - Tao, Wei. PY - 2012/5/22. Y1 - 2012/5/22. N2 - rRNA genes (rDNA) exist in two distinct epigenetic states, active promoters being unmethylated and marked by euchromatic histone modifications, whereas silent ones are methylated and exhibit heterochromatic features. Here we show that the nucleosome remodeling and deacetylation (NuRD) complex establishes a specific chromatin structure at rRNA genes that are poised for transcription activation. The promoter of poised rRNA genes is unmethylated, associated with components of the preinitiation complex, marked by bivalent histone modifications and covered by a nucleosome in the off position, which is refractory to transcription ...
Boundaries between different chromatin states must be maintained for stable gene expression patterns [1], [2]. Although many different chromatin states have been described, the two most fundamental categories are active euchromatin and silent heterochromatin [3]. Constitutive heterochromatin is associated with H3K9me2/3, HP1, and low histone turnover [4], [5]. Although generally inactive, heterochromatin may be transcribed during defined periods of the cell cycle, but the resulting transcripts are degraded [6], [7], [8]. The fission yeast Schizosaccharomyces pombe uses several alternative heterochromatin formation pathways in different regions that may substitute for one another. The RNAi pathway, which involves the proteins Dcr1 and Ago1, is the predominant mechanism used to nucleate heterochromatin [9], [10]. RNAi‐independent heterochromatin formation depends on transcription and RNA surveillance by factors such as Mlo3‐TRAMP [11]. The constitutive heterochromatin regions in S. pombe are ...
Global alterations in histone acetylation levels have been observed in both normal and cancer cells and can be prognostic of clinical outcome. However, unlike site-specific acetylation changes that can affect transcription of particular genes, the reason for genome-wide changes has been less clear. Because acetyl-coA molecules required for histone acetylation and acetate anions generated by histone deacetylation are required for many metabolic processes, McBrian and colleagues hypothesized that metabolic or physiologic cues might affect global histone acetylation levels. Systematic testing of the effects of culture medium components on histone acetylation revealed that decreased sodium bicarbonate concentrations resulting in lowered extracellular and intracellular pH led to a rapid, marked reduction in total levels of histone H3 and H4 acetylation at multiple lysine residues. These pH-dependent changes were specific to histone acetylation, as histone methylation was unaffected and required ...
The well‐known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS‐1/TRR‐1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans. Our results show that these beneficial effects are largely mediated through transcriptional up‐regulation of the FOXO transcription factor DAF‐16. MYS‐1 and TRR‐1 are recruited to the promoter regions of the daf‐16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes oxidative stress resistance by up‐regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to ...
The term epigenetic refers to heritable changes regulating gene expression that are not a result of changes in the primary DNA sequence. In cancer, aberrant epigenetic silencing of tumour-suppressor genes is a common occurrence that is associated with abnormal DNA methylation patterns and changes in covalent histone modifications [1]. These histone modifications, including acetylation, methylation and phosphorylation, play major roles in the regulation of chromatin structure and gene transcription [1], with each modification having a context-dependent association with transcriptional activation or repression. For example, H3K4 (histone H3 Lys4) methylation is associated with transcriptional activation, whereas H3K9 (histone H3 Lys9) methylation is associated with transcriptional repression. Histone methylation is catalysed by HMTs (histone methyltransferases), and methyl marks are removed by the catalytic activity of enzymes such as the FAD-dependent LSDs (lysine-specific demethylases) LSD1 ...
Author Summary Histones are the main protein components of chromatin. The N-terminal tails of histones stick out from the nucleosomes, the building blocks of chromatin, and are involved in the regulation of all DNA-dependent processes. Only Histone H2A has an additional C-terminal tail and currently very little is known about the function of this tail. The H2A C-terminus protrudes from the nucleosome and is located where the DNA enters and leaves the nucleosome. We show here that it can interact with the linker histone H1 that is important for higher order chromatin structure. We also find that this tail is involved in regulating nucleosome dynamics and mobility of H2A itself. The C-terminal H2A tail has also an important function in regulating the activity of chromatin remodelers, enzymes that can reposition nucleosomes. Furthermore we find that cells expressing C-terminally truncated H2A are more sensitive to stress, demonstrating that this tail is important for cellular homeostasis. Together our
Chromatin is the template on which DNA-associated transactions take place in eukaryotic organisms. Nucleosomes consisting of the four histones H2A, H2B, H3 and H4 each organize 150bp of DNA and constitute a first layer of chromatin. The three-dimensional organization of chromatin as well as histone post-translational modifications (PTMs) regulate recruitment of chromatin-associated effector proteins (effectors). Heterochromatin protein 1 (HP1) is an effector associated with silenced genome regions. HP1 recognizes histone H3 trimethylated at lysine 9 (H3 K9me3) and can dimerize. This results in a protein with two binding domains allowing multivalent engagement of target chromatin. HP1 can further promote chromatin condensation and inter-fiber contacts. The effector p53 binding protein (53BP1) is a key regulator in the DNA damage repair pathway. It is known to target a trio of PTMs; H4 dimethylated at K20 (H4 K20me2), H2A(.X) ubiquitylated at K15 (H2A.X K15ub) and H2A.X phosphorylated at S139 ...
Chromatin compacts DNA to an extreme extend and allows eukaryotic genome fit the size of the nucleus. On the other hand, however, it must process the ability to untighten DNA and to permit the cellular machinery access to genome. Chromatin consists of nucleosomes in which a protein core is constituted by four canonical histones H2A, H2B, H3, H4 and wrapped around by 147 bp of DNA. Histone variants, and the chromatin remodelling machinery, can reorganize the compaction of chromatin and thus be important for epigenetic regulation of gene expression.. Histone variant H2A.Z is a universal mark of dynamic nucleosomes. H2A.Z is essential for growth, development and viability of a number of species including mammals. H2A.Z plays critical roles in multiple biological processes including gene transcription and replication, DNA repair, and genome integrity. The chromatin incorporation of H2A.Z is catalysed by SRCAP, an ATP-dependent, multi-component chromatin remodelling complex. The YL1 subunit of SRCAP ...
The excision of mutagenic DNA adducts by the nucleotide excision repair (NER) pathway is essential for genome stability, which is key to avoiding genetic diseases, premature aging, cancer and neurologic disorders. Due to the need to process an extraordinarily high damage density embedded in the nucleosome landscape of chromatin, NER activity provides a unique functional caliper to understand how histone modifiers modulate DNA damage responses. At least three distinct lysine methyltransferases (KMTs) targeting histones have been shown to facilitate the detection of ultraviolet (UV) light-induced DNA lesions in the difficult to access DNA wrapped around histones in nucleosomes. By methylating core histones, these KMTs generate docking sites for DNA damage recognition factors before the chromatin structure is ultimately relaxed and the offending lesions are effectively excised. In view of their function in priming nucleosomes for DNA repair, mutations of genes coding for these KMTs are expected to cause
Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an
Histone acetylation is a hallmark of chromatin that has an open structure that can be accessed by DNA and RNA polymerases as well as transcription factors, resulting in the activation of gene transcription (Filippakopoulos and Knapp, 2014). Correspondingly, histone methylation increases the basicity and hydrophobicity of histone tails and the affinity of certain proteins, such as transcription factors, toward DNA (Teperino et al., 2010), thus affecting the gene expression. In this database, we have collected 584 non-redundant protein data of 8 organisms including H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, A. thaliana, S. pombe and S. cerevisiae from the literature. The data are further classified into 15 families for histone acetylation writers, erasers and readers and 32 families for histone methylation writers, erasers and readers, respectively. WERAM 1.0 is a comprehensive Eukaryotic Writers, Erasers and Readers protein of Histone Acetylation and Methylation system ...
Our collaboration with the group of Prof. Zheng on histone acetylation has led to a combined experimental/computational paper available from the Journal of Biological Chemistry.
Single Donor Human Buffy Coats Leukocytes from Innovative Research was used in the following study: Coupling Fluorescence-Activated Cell Sorting and Targeted Analysis of Histone Modification Profiles in Primary Human Leukocytes Jeannie M. Camarillo, Suchitra Swaminathan, Nebiyu A. Abshiru, Jacek W. Sikora, Paul M. Thomas, Neil L. Kelleher Journal of The American Society for Mass Spectrometry 08 July 2019 …Histone posttranslational modifications (PTMs) are essential for regulating chromatin and maintaining gene expression throughout cell differentiation. Despite the deep level of understanding of immunophenotypic differentiation pathways in hematopoietic cells, few studies have investigated global levels of histone PTMs required for differentiation.... ...
Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large amounts of starting material, and involves tedious processing of each individual sample. Here, we address these limitations with a technology that leverages DNA barcoding to profile chromatin quantitatively and in multiplexed format. We concurrently map relative levels of multiple histone modifications across multiple samples, each comprising as few as a thousand cells. We demonstrate the technology by monitoring dynamic changes following inhibition of p300, EZH2, or KDM5, by linking altered epigenetic landscapes to chromatin regulator mutations, and by mapping active and repressive marks in purified human hematopoietic stem cells. Hence, this technology enables quantitative studies ...
The N-terminal tail of CENP-A is highly divergent from other H3 variants. Canonical histone N-termini are hotspots of conserved post-translational modification; however, no broadly conserved modifications of the vertebrate CENP-A tail have been previously observed. Our lab has identified novel post-translational modifications on human CENP-A N-termini using high-resolution MS. These include the trimethylation of Gly1 at the alpha-amino position and side-chain phosphorylation of Ser16 and Ser18. CENP-A is subjected to constitutive initiating methionine removal, similar to other H3 variants. The nascent N-terminal residue Gly1 becomes trimethylated on the α-amino group. We identified the methyltransferase NRMT as the enzyme responsible for modifying the CENP-A amino terminus. Methylation occurs in the pre-nucleosomal form and marks the majority of CENP-A nucleosomes. Serine 16 and 18 become phosphorylated in pre-nucleosomal CENP-A and are phosphorylated on asynchronous and mitotic nucleosomal ...
TY - JOUR. T1 - Histone H2B mono-ubiquitylation maintains genomic integrity at stalled replication forks. AU - Northam, Matthew R.. AU - Trujillo, Kelly M.. N1 - Funding Information: National Institute of Health [K22-CA163485] as well as an Institutional Research Grant from the American Cancer Society [124175-IRG-13-041-01-IRG]; Publisher Copyright: © 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.. PY - 2016/11/2. Y1 - 2016/11/2. N2 - Histone modifications play an important role in regulating access to DNA for transcription, DNA repair and DNA replication. A central player in these events is the mono-ubiquitylation of histone H2B (H2Bub1), which has been shown to regulate nucleosome dynamics. Previously, it was shown that H2Bub1 was important for nucleosome assembly onto nascent DNA at active replication forks. In the absence of H2Bub1, incomplete chromatin structures resulted in several replication defects. Here, we report new evidence, which ...
Results High-risk GISTs harboured increased numbers of somatic mutations compared with low-risk GISTs (25.2 mutations/high-risk cases vs 6.8 mutations/low-risk cases; two sample t test p=3.1×10−5). Somatic alterations in the SETD2 histone modifier gene occurred in 3 out of 9 high-risk/metastatic cases but no low/intermediate-risk cases. Prevalence screening identified additional SETD2 mutations in 7 out of 80 high-risk/metastatic cases but no low/intermediate-risk cases (n=29). Combined, the frequency of SETD2 mutations was 11.2% (10/89) and 0% (0/34) in high-risk and low-risk GISTs respectively. SETD2 mutant GISTs exhibited decreased H3K36me3 expression while SETD2 silencing promoted DNA damage in GIST-T1 cells. In gastric GISTs, SETD2 mutations were associated with overexpression of HOXC cluster genes and a DNA methylation signature of hypomethylated heterochromatin. Gastric GISTs with SETD2 mutations, or GISTs with hypomethylated heterochromatin, showed significantly shorter relapse-free ...
Our previous studies showed that histones H2A and H2B, but not histones H3 or H4, displaced lamin Dm0 binding to chromosomes in vitro (Goldberg et al., 1999). Here we show a direct binding of histone H2A to B-type lamins from Drosophila and C. elegans. The sequences required for that binding are both highly restricted and located in regions plausibly involved in such interactions in vivo. Thus, the lamin sequences are in a linker region between two structured domains, which is likely to be available for interaction in vivo, and this direct binding requires the NLS of lamins, similarly to their binding to chromosomes.. The amino and carboxyl tail domains of histone H2A are each necessary, but not sufficient, for histone H2A binding to lamin Dm0. Histone H2A is unique among core histones in having its C-terminal tail, in addition to its N-terminal tail, exposed at the nucleosomal surface, thus being more accessible to posttranslational modifications and for binding protein partners, such as lamins ...
The process of histone acetylation at lysine residues by histone acetyltransferase (HAT) is an important epigenetic marker and can be measured with the use of histone lysine acetylation antibodies . Acetylation of histones...
We analyse chromosome location of H3 and H4 histone gene clusters by fluorescence in-situ hybridization (FISH) in 35 species of Acrididae grasshoppers belonging to seven subfamilies. As in other organ
Posttranslational modifications of histones, ATP-dependent chromatin remodeling, and incorporation of histone variants are three major events to regulate DNA dependent processes in chromatin context.; Histones are the major protein components within chromatin, and epigenetic modifications of these proteins play a vital role in transcription. Acetylation and methylation of core histones are two major modifications, which are introduced by histone acetyltransferases (HATs) and histone methyltransferases (HMTs). Albeit the mechanism of action has not been identified, it has been proposed that these two modifications regulate gene transcription through facilitating recruitment of regulatory factors to the target genes. As a first step to investigate recruitment-based contribution of histone tails and their modifications in transcription, I have generated HeLa cell lines that stably express H3 tails for the biochemical purification of H3 tail-associated complex. The purified complex contains multiple ...
Posttranslational modification of histone protein plays critical regulatory roles for eukaryotic genomes. DNA is packaged by an octamer of histone subunits (two each of H2A, H2B, H3, and H4) to form a nucleosome (Luger et al., 1997). Histone acetylation influences DNA-templated reactions, defines chromosomal features, shapes nuclear architecture, and underlies epigenetic phenomena (Earley et al., 2006; Shahbazian and Grunstein, 2007; Yang and Seto, 2007; Venkatesh and Workman, 2015). In the context of transcription, acetylated histone is generally thought to promote transcription initiation by reducing histone-DNA affinity and recruiting transactivators, whereas deacetylation facilitates compaction and silencing (Struhl, 1998). Acetylation is catalyzed by histone acetyltransferases and removed by histone deacetylases (HDACs). Genome sequencing of the flowering plant Arabidopsis (Arabidopsis thaliana) revealed eighteen putative HDACs falling into three families: 12 are members of the Reduced ...
The study of DNA templated events is not complete without considering the chromatin environment. Histone modifications help to regulate gene expression, chromatin compaction and DNA replication. Because DNA damage repair must occur within the context of chromatin, many remodeling enzymes and histone modifications work in concert to enable access to the DNA and aid in restoration of chromatin after repair is complete. CK2 has recently been identified as a histone modifying enzyme. In this study we identify CK2 as a histone H3 tail kinase in vitro, identify the phospho-acceptor site in vitro, and characterize the modification in vivo in S. cerevisiae. We also characterize the DNA damage phenotype of a strain lacking a single catalytic subunit of CK2. We further characterize the CK2- dependent phosphorylation of serine 1 of histone H4 in vivo. We find that it is recruited directly to the site of a DSB and this recruitment requires the SIN3/RPD3 histone deacetylase complex. We also characterize the
In many eukaryotes, histone gene expression is regulated in a cell cycle-dependent manner, with a spike pattern at S phase. In fission yeast the GATA-type transcription factor Ams2 is required for transcriptional activation of all the core histone genes during S phase and Ams2 protein levels per se show concomitant periodic patterns. We have recently unveiled the molecular mechanisms underlying Ams2 fluctuation during the cell cycle. We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability. Intriguingly, Ams2 proteolysis requires Hsk1-a Cdc7 homologue in fission yeast generally called Dbf4-dependent protein kinase (DDK)-and the SCF ubiquitin ligase containing the substrate receptor Pof3 F-box protein. Here, we discuss why histone synthesis has to occur only during S phase. Our results indicate that excess synthesis of core histones outside S phase results in deleterious effects on cell survival. In particular, functions
Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.. Read more → ...
From NCBI Gene:. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]. From UniProt: ...
From NCBI Gene:. Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]. From UniProt: ...
Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression.
Eukaryotic genomes are packaged into a complex structure known as chromatin. The basic unit of chromatin is the nucleosome, which consists of two copies each of the histone proteins H2A, H2B, H3, and H4. The flexible N‐termini of histone proteins are subject to various posttranslational modifications associated with different types of chromatin. Originally defined cytologically as chromosome regions that do not undergo post‐mitotic decondensation but remain condensed during interphase, a distinct type of chromatin referred to as heterochromatin is generally characterized by histone hypoacetylation and specific methylation of lysine 9 of the histone H3 tail (H3K9me). This mark is a binding site for proteins containing a so‐called chromodomain (CD), such as proteins of the heterochromatin protein 1 (HP1) family that recognize and bind methylated H3K9 via their CDs (Eissenberg & Elgin, 2000; Bannister et al, 2001; Lachner et al, 2001).. HP1 proteins have long been thought to play a central ...
The development of breast cancer prevention strategies will be facilitated through a better understanding of the epigenetic regulation of the genome (i.e, a series of mechanisms resulting in the reorganization of chromatin, and including but not limited to posttranslational histone modifications and DNA methylation, and that control the expression and silencing of genes). An approach is to identify epigenetic factors that influence breast cancer onset in response to the environment. An initial focus is on nutrition since dietary patterns have been associated with breast cancer and nutrients are known to impact gene expression (nutrigenomics). This approach will be facilitated by the development of novel assessment methods of presymptomatic, normal appearing tissues. Once the diet-epigenetic interactions that protect or weaken the breast epithelium have been identified, it will be possible to develop effective breast cancer prevention strategies that will benefit from innovative methods of ...
Multipotent progenitor cells of the cerebral cortex balance self-renewal and differentiation to produce complex neural lineages in a fixed temporal order in a cell-autonomous manner. We studied the role of the polycomb epigenetic system, a chromatin-based repressive mechanism, in controlling cortical progenitor cell self-renewal and differentiation. We found that the histone methyltransferase of polycomb repressive complex 2 (PCR2), enhancer of Zeste homolog 2 (Ezh2), is essential for controlling the rate at which development progresses within cortical progenitor cell lineages. Loss of function of Ezh2 removes the repressive mark of trimethylated histone H3 at lysine 27 (H3K27me3) in cortical progenitor cells and also prevents its establishment in postmitotic neurons. Removal of this repressive chromatin modification results in marked up-regulation in gene expression, the consequence of which is a shift in the balance between self-renewal and differentiation toward differentiation, both directly to
Multipotent progenitor cells of the cerebral cortex balance self-renewal and differentiation to produce complex neural lineages in a fixed temporal order in a cell-autonomous manner. We studied the role of the polycomb epigenetic system, a chromatin-based repressive mechanism, in controlling cortical progenitor cell self-renewal and differentiation. We found that the histone methyltransferase of polycomb repressive complex 2 (PCR2), enhancer of Zeste homolog 2 (Ezh2), is essential for controlling the rate at which development progresses within cortical progenitor cell lineages. Loss of function of Ezh2 removes the repressive mark of trimethylated histone H3 at lysine 27 (H3K27me3) in cortical progenitor cells and also prevents its establishment in postmitotic neurons. Removal of this repressive chromatin modification results in marked up-regulation in gene expression, the consequence of which is a shift in the balance between self-renewal and differentiation toward differentiation, both directly to
Posttranslational histone modifications, DNA methylation patterns, and populations of small noncoding RNAs in sperm have been implicated in the transgenerational transmission of paternal experience, with changes in these epigenetic marks observed following male exposure to such diverse stimuli as stress, malnutrition, and drugs of abuse (11⇓⇓⇓⇓⇓⇓⇓⇓⇓-21). In particular, the role of sperm RNA as a mechanistic link between paternal experience and its consequences on offspring behavior and physiology has been emphasized by recent studies that characterize offspring phenotypes following in vitro fertilization and/or the experimental manipulation of total sperm RNA content (12, 20). In our model of paternal stress, a reduced HPA axis response in offspring was associated with the increased expression of nine miRs (miR-29c, miR-30a, miR-30c, miR-32, miR-193-5p, miR-204, miR-375, miR-5323p, and miR-698) in paternal sperm following chronic stress exposure (11). In the current study, to ...
Background Dot1L, a histone methyltransferase that targets histone H3 lysine 79 (H3K79), has been implicated in gene regulation and the DNA damage response although its functions in these processes remain poorly defined. Methodology/Principal Findings Using the chicken DT40 model system, we generated cells in which the Dot1L gene is disrupted to examine the function and focal recruitment of the 53Bp1 DNA damage response protein. Detailed kinetic and dose response assays demonstrate that, despite the absence of H3K79 methylation demonstrated by mass spectrometry, 53Bp1 focal recruitment is not compromised in these cells. We also describe, for the first time, the phenotypes of a cell line lacking both Dot1L and 53Bp1. Dot1L¿/¿ and wild type cells are equally resistant to ionising radiation, whereas 53Bp1¿/¿/Dot1L¿/¿ cells display a striking DNA damage resistance phenotype. Dot1L and 53Bp1 also affect the expression of many genes. Loss of Dot1L activity dramatically alters the mRNA levels of ...
Unmodified histone proteins such as H3 and H4 are useful for studying epigenetic mechanisms such as histone methylation, histone acetylation, and histone phosphorylation, which occur as a result of the modification to histone...
The linker histones H1/H5 bind to the entry and exit points of nucleosomal DNA and protect additional ~20 bp at one end. However, it is unclear whether there is any sequence feature at the ends of nucleosomal DNA facilitating the linker histone binding. T
Transcription regulation in pluripotent embryonic stem (ES) cells is a complex process that involves multitude of regulatory layers, one of which is post-translational modification of histones. Acetylation of specific lysine residues of histones plays a key role in regulating gene expression. Here we have investigated the genome-wide occurrence of two histone marks, acetylation of histone H3K9 and K14 (H3K9ac and H3K14ac), in mouse embryonic stem (mES) cells. Genome-wide H3K9ac and H3K14ac show very high correlation between each other as well as with other histone marks (such as H3K4me3) suggesting a coordinated regulation of active histone marks. Moreover, the levels of H3K9ac and H3K14ac directly correlate with the CpG content of the promoters attesting the importance of sequences underlying the specifically modified nucleosomes. Our data provide evidence that H3K9ac and H3K14ac are also present over the previously described bivalent promoters, along with H3K4me3 and H3K27me3. Furthermore, like
Background: Triptolide is a medicinal herb-derived diterpene triepoxide with potent anti-tumor activity against a wide range of tumors. The anti-tumor mechanism of this small molecule has been correlated mainly with its ability to inhibit and inactivate subunits of RNA polymerase II, thereby suppressing global gene transcription. Epigenetic imbalance including histone methylation are well known to play important role in Prostate cancer (PCa) onset and progression. The goal of this study was to investigate whether Triptolide performs its anti-PCa activities by reshaping the histone methylation landscape in PCa cells.Methods: Triptolide-treated PCa cell lines were analyzed by RT-qPCR and western blotting to measure the expression of histone methylases; demethylases and associated histone marks. Detection of senescence was done using Senescence Associated β-Galactosidase Staining. Apoptosis and cell cycle analysis were performed by flow cytometry. Senescence -associated heterochromatine foci were detected
Histones and their variants are subjected to several post-translational modifications (PTMs). Histones PTMs play an important role in the regulation of gene expression and are critical for the development and progression of many types of cancer, including breast cancer. In this study, we used two-dimensional TAU/SDS electrophoresis, coupled with mass spectrometry for a comprehensive profiling of histone PTMs in breast cancer cell lines.Proteomic approach allowed us to identify 85 histone PTMs, seventeen of which are not reported in the UniProt database. Western blot analysis was performed to confirm a peculiar pattern of PTMs in the sporadic and hereditary breast cancer cell lines compared to normal cells. Overlapping mass spectrometry data with western blotting results, we identified, for the first time to our knowledge, a tyrosine phosphorylation on histone H1, which is significantly higher in breast cancer cells. Additionally, by inhibiting specific signaling paths, such as PI3K, PPARγ and FAK
TY - JOUR. T1 - Prothymosin alpha interacts with C-terminal domain of histone H1 and dissociates p53-histone H1 complex. AU - Zakharova, N. I.. AU - Sokolov, V. V.. AU - Suvorova, A. A.. AU - Shiau, Ai Li. AU - Wu, Chao Liang. AU - Evstafieva, A. G.. N1 - Funding Information: This work was supported by grants from the Rus sian Foundation for Basic Research (10 04 92007 HHC_a and 09 04 01246 a), Russian Ministry of Education and Science (Contracts P334 and 14.740.11.0168), and National Science Council (Tai wan) NSC 99 2923 B 006 003 MY3.. PY - 2011/8. Y1 - 2011/8. N2 - A novel mode of tumor suppressor protein p53 regulation, mediated by recruitment of the linker histone H1 to the promoters of p53 target genes leading to specific repression of p53-dependent transcription, has recently been uncovered. Yet, how this repression could be relieved is not clear. Previously, a histone-binding nuclear protein prothymosin alpha (ProTa) was shown to trigger a p53 response. The histone-binding region of ...
Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1/H5 are known as the linker histones. The core ... Histone variants Chromatin Gene silencing Genetics Histone acetyltransferase Histone deacetylases Histone methyltransferase ... Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones. Histone proteins are among the most ... There are five families of histones which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The ...
Histone code Nucleosome Chromatin Other histone proteins: Histone H1 Histone H2A Histone H3 Histone H4 Bhasin M, Reinherz EL, ... Similar to other histone proteins, histone H2B has a distinct histone fold that is optimized for histone-histone as well as ... Two copies of histone H2B come together with two copies each of histone H2A, histone H3, and histone H4 to form the octamer ... histone H2B genes share a promoter region with sequences that code for histone H2A. While all genes in the histone cluster are ...
... s (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine ... Histone-Modifying Enzymes Histone acetyltransferase (HAT) Histone deacetylase (HDAC) RNA polymerase control by chromatin ... histone marks. Generally, the effect of a histone methyltransferase on gene expression strongly depends on which histone ... Histone methylation plays an important role in epigenetic gene regulation. Methylated histones can either repress or activate ...
There are five different histone proteins: H1, H2A, H2B, H3, and H4. A core histone is formed when two of each histone subtype ... Histone-modifying enzymes Histone deacetylase (HDAC) Histone methyltransferase (HMT) RNA polymerase control by chromatin ... Histone H1 locks the nucleosome complex together, and it is the last protein to bind in the complex. Histones tend to be ... Sas2 is also observed to acetylate H3K14 in vitro on free histones. Esa1 can also acetylate H3K14 in vitro on free histones as ...
The other histone proteins are: H1, H2B, H3 and H4. Histones are proteins that package DNA into nucleosomes. Histones are ... Histone H2A is composed of non-allelic variants. The term "Histone H2A" is intentionally non-specific and refers to a variety ... Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. ... There are five families of histones known to date; these histones are termed H1/H5, H2A, H2B, H3, and H4. H2A is considered a ...
These are denoted as Histone H3.1, Histone H3.2, Histone H3.3, Histone H3.4 (H3T), Histone H3.5, Histone H3.X and Histone H3.Y ... Acetylation of histone H3 at several lysine positions in the histone tail is performed by histone acetyltransferase enzymes ( ... H3F3B Histone code#Histone_H3 Nucleosome Histone Chromatin Bhasin M, Reinherz EL, Reche PA (2006). "Recognition and ... Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main ...
... is a protein in humans that is encoded by the H3C1 gene. Histones are basic nuclear proteins that are responsible ... 1991). "Isolation and characterization of two human H1 histone genes within clusters of core histone genes". Genomics. 10 (4): ... 2001). "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins". Nature. 410 (6824): 116-20. Bibcode: ... This gene is intronless and encodes a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, ...
... is a 102 to 135 amino acid protein which shares a structural motif, known as the histone fold, formed from three a- ... Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a ... Histone proteins are among the most highly conserved eukaryotic proteins. For example, the amino acid sequence of histone H4 ... This tetramer further combines with two H2a-H2b dimers to form the compact Histone octamer core. Histone H4 is one of the ...
Nucleosome Histone Chromatin Linker histone H1 variants Other histone proteins involved in chromatin: H2A H2B H3 H4 ... Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though ... H1 is less conserved than core histones. The globular domain is the most conserved part of H1. Unlike the other histones, H1 ... Like other histones, the histone H1 family is extensively post-translationally modified (PTMs). This includes serine and ...
A histone fold is a structurally conserved motif found near the C-terminus in every core histone sequence in a histone octamer ... Histone folds play a role in the nucleosomal core particle by conserving histone interactions when looking at interface ... Similarly modes 5 and 7 of the core nucleosome particle use two types of histone fold dimers which show that all histone ... Baxevanis, Andreas D.; Landsman, David (1 January 1997). "Histone and histone fold sequences and structures: a database". ...
Histone acetyltransferase (HAT) Histone deacetylase inhibitor Histone methyltransferase (HMT) Histone-modifying enzymes RNA ... Histone deacetylases remove those acetyl groups, increasing the positive charge of histone tails and encouraging high-affinity ... A decrease in a HDAC would cause greater presence of acetylation on histone tails. Histone acetylation is associated with ... Atm mutation causes neurons to accumulate nuclear histone deacetylase 4 (HDAC4) resulting in increased histone deacetylation ...
Histone Histone-modifying enzymes Jenuwein T, Allis C (2001). "Translating the histone code". Science. 293 (5532): 1074-80. ... Histone Modifications with function and attached references Histone Code Overview sheet Histone Modification ... 2011). "Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification". Cell. 146 ( ... Structural determinants of histone recognition by readers, writers and erasers of the histone code are revealed by a growing ...
The histone octamer interacts with the DNA through both its core histone folds and N-terminal tails. The histone fold interacts ... Heterodimers, or histone-only intermediates are formed from histone-fold domains. The formation of histone only-intermediates ... Each histone has both an N-terminal tail and a C-terminal histone-fold. Each of these key components interacts with DNA in its ... Each histone in the octamer has an N-terminal tail that protrudes from the histone core. The tails play roles both in inter and ...
Histone code Histone acetylation and deacetylation Histone methyltransferase Methylation Methyllysine Genetic Imprinting Kramer ... Histone methylation is a process by which methyl groups are transferred to amino acids of histone proteins that make up ... Methylation of histones can either increase or decrease transcription of genes, depending on which amino acids in the histones ... The activities of histone methyltransferases are offset by the activity of histone demethylases. This allows for the switching ...
... may refer to: Demethylase (Histone-H3)-lysine-36 demethylase This disambiguation page lists articles ... associated with the title Histone demethylase. If an internal link led you here, you may wish to change the link to point ...
The Histone Database is a comprehensive database of histone protein sequences including histone variants, classified by histone ... The creation of the Histone Database was stimulated by the X-ray analysis of the structure of the nucleosomal core histone ... Marino-Ramirez L, Hsu B, Baxevanis AD, Landsman D (2006). "The Histone Database: a comprehensive resource for histones and ... Baxevanis AD, Landsman D (1997). "Histone and histone fold sequences and structures: a database". Nucleic Acids Res. 25 (1): ...
macroH2A contains a histone fold domain and an extra, long C-terminal macro domain which can bind poly-ADP-ribose. This histone ... Histone variants are proteins that substitute for the core canonical histones (H3, H4, H2A, H2B) in nucleosomes in eukaryotes ... Histone H3.3 has been found to play an important role in maintaining genome integrity during the mammalian development. Histone ... "Histome: The Histone Infobase" is manually curated database of histone variants in humans and associated post-translational ...
In chromatin, those proteins which remain after the histones have been removed, are classified as non-histone proteins. The non ... Non-histone protein are acidic. Chromatin Cohesin Condensin Fedele, Monica (2006). Encyclopedic reference of genomics and ... histone proteins, are a large group of heterogeneous proteins that play a role in organization and compaction of the chromosome ... Heterochromatin Protein 1 and Polycomb are common non-histone proteins. This classification group also includes numerous other ...
... is a protein that in humans is encoded by the H2AZ1 gene. Histones are basic nuclear proteins that are ... Histone H2AZ is a variant of histone H2A, and is used to mediate the thermosensory response, and is essential to perceive the ... PDBe-KB provides an overview of all the structure information available in the PDB for Human Histone H2A.Z v t e (Articles with ... "Entrez Gene: H2AFZ H2A histone family, member Z". Bargaje R., Alam P., Patowary A., Sarkar M., Ali T., Gupta S., Garg M., Singh ...
... through modulating the acetylation/deacetylation of histones and/or non-histone proteins such as transcription factors. Histone ... Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs ... Histone deacetylase inhibition induces the accumulation of hyperacetylated nucleosome core histones in most regions of ... Based on their homology of accessory domains to yeast histone deacetylases, the 18 currently known human histone deacetylases ...
... (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase ... This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein ... March 2014). "Regulation of acetylation of histone deacetylase 2 by p300/CBP-associated factor/histone deacetylase 5 in the ... Seto E, Yoshida M (April 2014). "Erasers of histone acetylation: the histone deacetylase enzymes". Cold Spring Harbor ...
Histone acetylation, or the addition of an acetyl group to histones, is facilitated by histone acetyltransferases (HATs) which ... Much like histone acetylation, histone phosphorylation neutralizes the negative charge on histones which induces euchromatin ... DNA Histone Nucleosome Chromatin Euchromatin Heterochromatin Histone acetylation and deacetylation Histone methylation Protein ... Histone deacetylases (HDACs) facilitate the removal of such groups. The positive charge on a histone is always neutralized upon ...
... is an enzyme that in humans is encoded by the HDAC5 gene. Histones play a critical role in ... The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase ... "Entrez Gene: HDAC5 histone deacetylase 5". McGee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD, Kemp BE, Hargreaves ... Huang Y, Tan M, Gosink M, Wang KK, Sun Y (May 2002). "Histone deacetylase 5 is not a p53 target gene, but its overexpression ...
... target 5 major classes of histone protein subunits: H1, H2A, H2B, H3, and H4. Anti-histone antibodies ... Highly modified histones have been shown to prompt a greater immune response. Anti-histone antibodies can be clinically ... which specifically target histone protein subunits or histone complexes. They were first reported by Henry Kunkel, H.R. Holman ... anti-histone antibodies are present. Anti-histone antibodies may also be present in Alzheimer's disease and dementia patients. ...
... including H1 histones, with the aim of producing informative and easily searchable histone variant names. histone H1 histone ... oocyte specific variants Histone H1 differs strongly from the core histones. Rather than originating from archaeal histones, it ... H1 histones bind to the linker DNA exiting from the nucleosome core particle, while the core histones (H2A, H2B, H3 and H4) ... Unlike core histones featuring a so-called histone fold, H1s typically have a short basic N-terminal domain, a globular domain ...
The NuA4 histone acetyltransferase complex is a protein complex that has histone acetylase activity on chromatin, as well as ... All four conserved lysines of histone H4 can be acetylated by NuA4. The catalytic subunit of the complex has been identified as ... Purification and characterization of a native multi-subunit complex (NuA4) from yeast that acetylates nucleosomal histone H4 ... "Gene Ontology Term: NuA4 histone acetyltransferase complex". Saccharomyces Genome Database. Allard S, Utley RT, Savard J, ...
These proteins are of the chaperone protein group and in particular can be placed into the histone chaperone subgroup. ASF1 ... In molecular biology, the ASF1 like histone chaperone family of proteins includes the yeast and human ASF1 proteins. ... "Structure and function of the conserved core of histone deposition protein Asf1". Curr. Biol. 13 (24): 2148-58. doi:10.1016/j. ... "A human homologue of yeast anti-silencing factor has histone chaperone activity". Genes Cells. 5 (3): 221-33. doi:10.1046/j. ...
Histone acetyltransferase Histone deacetylase Histone methylation Acetylation Phosphorylation Nucleosome Watson JD, Baker TA, ... These histone cores are composed of 8 subunits, two each of H2A, H2B, H3 and H4 histones. This protein complex forms a ... Unlike histone core proteins, histone tails are not part of the nucleosome core and are exposed to protein interaction. A model ... By deacetylating the histone tails, the DNA becomes more tightly wrapped around the histone cores, making it harder for ...
... (EC, histone protein methylase I, nuclear protein (histone) N-methyltransferase ... Histone-arginine+N-methyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology ( ... Dual substrate specificity for S-adenosylmethionine:histone-arginine N-methyltransferase". The Journal of Biological Chemistry ... This enzyme catalyses the following chemical reaction S-adenosyl-L-methionine + histone-arginine ⇌ {\displaystyle \ ...
Page for Histone 3′ UTR stem-loop at Rfam Transterm page for Histone 3′ stem loop UTRSite page for Histone 3′UTR stem-loop ... The histone 3′ UTR stem-loop is an RNA element involved in nucleocytoplasmic transport of the histone mRNAs, and in the ... "Structure of the histone mRNA hairpin required for cell cycle regulation of histone gene expression". RNA. 8 (1): 29-46. doi: ... The mRNAs of metazoan histone genes lack polyadenylation and a poly-A tail, instead 3′ end processing occurs at a site between ...
... Nat Struct Mol Biol. 2014 Aug;21(8):651-2. doi: 10.1038/nsmb.2864. ...
Table 2. Summary of the activities of histone deacetylase inhibitors in endometriotic lesions and other cell/tissues. Name of ... Many in vitro, in vivoand clinical studies have shown that histone deacetylase inhibitors (HDACIs) are promising in treating ... The desirable properties of histone deacetylase inhibitors as therapeutics for treating endometriosis are enumerated, and the ... The desirable properties of histone deacetylase inhibitors (HDACIs) as therapeutics for treating endometriosis are enumerated ...
Scientists show how roundworm daughter cells remember the histone modification patterns of their parents. ... Heritable Histones. Scientists show how roundworm daughter cells remember the histone modification patterns of their parents.. ... "When you replicate the DNA you have to replicate the histones . . . and de novo synthesized histones dont have marks put there ... a histone-modifying enzyme that methylates lysine 27 of histone H3 (H3K27me)-a mark associated with transcriptional repression ...
This study found that the SARS-CoV-2 protein ORF8 disrupts host epigenetic regulation through histone mimicry. ... Histone proteins are major determinants of gene regulation, and histone mimicry allows viruses to gain control of gene ... Viruses that lacked ORF8 or the histone mimic site had a reduced ability to disrupt host chromatin, and host cells infected ... uncover that the viral ORF8 protein mimics the H3 histone protein to disrupt epigenetic regulation. The authors found that, ...
Histone H3 in silent DNA had a "methyl" group attached to a particular lysine amino acid, #9. Histone H3 in active DNA had a ... "histone code" exists in which differentially modified histone proteins can organize the genome into active and silent regions ... Histones bind to DNA and wrap the genetic material into "beads on a string" in which DNA (the string) is wrapped around small ... The new study in Science is one of several that are beginning to elucidate the role of histones and other proteins in such a ...
The newly developed scChIX-seq protocol supports profiling multiple histone modifications in single cells to double your ... Two target individual histone modifications, and a third targets both histone modifications in the same cell ... Profiling two histone modifications in single cells with scChIX-seq involves the generation of three genome-wide sortChIC-seq ... Each double-incubated cell becomes assigned to the most probable pair of cell states, one from each histone modification, and ...
Home Topics Cancer PrognosDx and Accium to Work on Histone Biomarker Cancer Tests ... The firm has in addition generated a confidential list of drugs that may be stratified using the tissue-based histone ... PrognosDx Health and Accium BioSciences are teaming up to co-develop and commercialize a series of predictive histone biomarker ... PrognosDx is exploiting expertise in tissue-based global cellular histone biomarkers to develop tools that provide clinicians ...
Linker histone H1 is a major chromatin structural protein that facilitates higher-order chromatin folding. By analyzing the ... We present evidence that H1 participates in mediating changes of histone marks and DNA methylation necessary for silencing ...
A recent histone modification study led by Broad Institute researchers demonstrates the potential of high-resolution mass ... "These histone marks are not just about disease. They are also about fine control of how the genome gets expressed in many ... Histone Modification Study Demonstrates Potential of High-resolution Targeted Proteomics Oct 05, 2013 , Adam Bonislawski ... A recent histone modification study led by Broad Institute researchers demonstrates the potential of high-resolution mass ...
... antibody to their growing line of EpiPlusTM histone modification antibodies. Over the past... ... Novus added a new Histone H3 [dimethyl Lys9/phospho Thr6] ... New Histone H3 [dimethyl Lys9/phospho Thr6] Antibody Released. ... The new Histone H3 [dimethyl Lys9/phospho Thr6] Antibody (NB21-1053) has been validated for Western blot, ChIP, dot blot, and ... Littleton, CO, September 21, 2011 --( Today, Novus added a new Histone H3 [dimethyl Lys9/phospho Thr6] antibody to ...
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CRYSTAL STRUCTURE OF THE HISTONE HMFA FROM METHANOTHERMUS FERVIDUS ... PROTEIN (HISTONE HMFA). A, B. 68. Methanothermus fervidus. Mutation(s): 0 Gene Names: hmfA. ... As prolines are present at these positions in all archaeal histone sequences, this proline-tetrad structure is likely to be a ... NMR Structure of Hmfb from the Hyperthermophyle, Methanothermus Fervidus, Confirms that This Archaeal Protein is a Histone. ...
Histone deacetylase inhibitors have been shown to induce changes in gene expression, affecting cell cycle regulation, ... The relatively new therapeutic option with the use of histone deacetylase inhibitors is being advanced in the hope of ... Histone acetylation is regulated by the addition of acetyl-CoA via the opposing actions of histone acetyltransferases (HATs) ... C. L. Peterson and M. A. Laniel, "Histones and histone modifications," Current Biology, vol. 14, no. 14, pp. R546-551, 2004. ...
Recent work has highlighted the possible contribution of post-translational modifications of histones via histone deacetylases ... HDACs remove the acetyl group on histones and work synchronously with other histone-modifying enzymes to regulate gene ... reports of long-lasting histone hypoacetylation due to HDAC and histone acetyltransferase dysfunction after stroke (Park and ... Delayed Treatment with Histone Deacetylase Inhibitors Promotes Stroke Recovery Message Subject (Your Name) has forwarded a page ...
Archaeal histone. Timeline for Protein Archaeal histone from a.22.1.2: Archaeal histone: *Protein Archaeal histone from a.22.1. ... Protein Archaeal histone from a.22.1.2: Archaeal histone appears in SCOP 1.67. *Protein Archaeal histone from a.22.1.2: ... Archaeal histone appears in SCOP 1.71. *Protein Archaeal histone from a.22.1.2: Archaeal histone appears in the current release ... Fold a.22: Histone-fold [47112] (1 superfamily). core: 3 helices; long middle helix is flanked at each end with shorter ones. ...
Highly specific and rigorously validated in-house, Histone H2B (53H3) Mouse Monoclonal Antibody (CST #2934) is ready to ship. ... Histone H2B (53H3) Mouse mAb detects endogenous levels of total histone H2B protein. This antibody does not cross-react with ... The p300/CBP histone acetyltransferases acetylate multiple lysine residues in the amino terminal tail of histone H2B (Lys5, 12 ... Hyper-acetylation of the histone tails neutralizes the positive charge of these domains and is believed to weaken histone-DNA ...
Histone H3 peptide (Tri-methylated K9), biotin; Study enzyme kinetics, and screen small molecular inhibitors of JMJ for drug ... Histone H3 peptide tri-methylated at Lysine 9, biotinylated, substrate for histone demethylases belonging to the Jumanji domain ...
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Histones play a major role in this. "Histones are proteins around which our DNA is wrapped and which thus serve to package the ... Going fishing in the protein pond using histones as a bait - how do cells decide how to repair their DNA?. ... The focus is on the so-called "histone proteins" on which the DNA strands are wound and that can determine whether a gene can ... "Put simply, we build a molecular bait with defined histones and use it to go fishing in the nucleus - and then it gets exciting ...
The histones are divided into fractions, with each fraction having a distinct amino acid composition and sequence. Histones are ... Histones are a group of similar, small, highly conserved nuclear proteins that bind to DNA by their many basic residues. ... Histones are also classified by relatively high levels of lysine and arginine. The presence of autoantibodies to histones are ... "Histone Nomenclature in the Structure and Function of Chromatin." (Fitzsimmins, D. W, and Walstenholme, G.E. W., eds.) CIBA ...
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View Mouse Monoclonal anti-Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) (NBP1-30141). Validated Applications: WB, ChIP, ELISA ... Western Blot: Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) [NBP1-30141] - Analysis of Histone H3 K9-me3 in HeLa histone ... Home » Histone H3 » Histone H3 Antibodies » Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) ... Blogs on Histone H3. Showing 1-10 of 11 blog posts - Show all blog posts.. Check out the latest blog posts on Histone H3. ...
Histone deacetylases have central functions in regulating stress defenses and development in plants. However, the knowledge ... In this study, we determined the proteome-wide signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis. ... Furthermore, our analysis revealed that histone deacetylase 14 (HDA14) is the first organellar-localized RPD3/HDA1 class ... which are potential substrates of the RPD3/HDA1-like histone deacetylases in Arabidopsis, of which at least 30 of these ...
histone cell cycle regulator (hira) gene expression in Xenopus laevis embryo. , assayed via in situ hybridization, NF stage 2, ...
Histone acetylation is a reversible reaction that occurs on the lysine residues of histone tails. Histone acetyltransferases ( ... Histone acetylation plays an important role in the modulation of chromatin condensation and transcriptional regulation. ... Mass Spectroscopy Profiling of Histone Modifications. * Inflammaging - What Epigenetic Associations with Kidney Health Can ... HATs) catalyze the transfer of an acetyl group from acetyl coenzyme A, while histone deacetylases (HDACs) perform the ...
Identifying genome-wide transcription units from histone modifications using EPIGENE With the successful completion of the ... that models the observed combination of histone modifications using a product of independent Bernoulli random variables to ... a novel chromatin segmentation method for identifying genome-wide active TUs using transcription-associated histone ... problem can be alleviated by chromatin-based approaches due to a well-established correlation between transcription and histone ...
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Vorinostat is a histone deacetylase (HDAC) inhibitor. HDAC inhibition results in hypoacetylation of core nucleosomal histones, ... Antineoplastic Agents, Histone Deacetylase Inhibitors. Class Summary. These agents can induce the termination of cell growth, ... Belinostat is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from the lysine residues of ... Belinostat, a novel pan-histone deacetylase inhibitor (HDACi), in relapsed or refractory peripheral T-cell lymphoma (R/R PTCL ...
  • Class I Histone Deacetylases Inhibitors " has 18 results in Products. (
  • Histone deacetylases have central functions in regulating stress defenses and development in plants. (
  • In this study, we determined the proteome-wide signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis. (
  • Relative quantification of the changes in the lysine acetylation levels was determined on a proteome-wide scale after treatment of Arabidopsis leaves with deacetylase inhibitors apicidin and trichostatin A. We identified 91 new acetylated candidate proteins other than histones, which are potential substrates of the RPD3/HDA1-like histone deacetylases in Arabidopsis, of which at least 30 of these proteins function in nucleic acid binding. (
  • Histone acetyltransferases (HATs) catalyze the transfer of an acetyl group from acetyl coenzyme A, while histone deacetylases (HDACs) perform the antagonistic action of removing the acetyl group. (
  • Dr. Westendorf's Skeletal Development and Regeneration Research Laboratory is studying histone deacetylases in bone development and bone diseases. (
  • Improved understanding of the molecular mechanisms by which small-molecule inhibitors of histone deacetylases (HDAC) induce programs, such as cellular differentiation and apoptosis, would undoubtedly assist their clinical development as anticancer agents. (
  • The small-molecule inhibitors of class I and II histone deacetylases (HDAC) have lately received much attention due to their promising clinical application as antitumor agents ( 1 - 3 ). (
  • Myc oncoproteins and histone deacetylases (HDACs) modulate gene transcription and enhance cancer cell proliferation, and HDAC inhibitors are among the most promising new classes of anticancer drugs. (
  • Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. (
  • Histone acetylation is a reversible reaction that occurs on the lysine residues of histone tails. (
  • Histone acetylation plays an important role in the modulation of chromatin condensation and transcriptional regulation. (
  • Histone modification represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms and it includes methylation, acetylation, phosphorylation and ubiquitination [ 4 ]. (
  • More and more evidence suggest that histone modifications (such as methylation and acetylation) can serve as a binding platform to attract other protein complexes to chromatin [ 5 - 7 ]. (
  • Both DNA and histone proteins are prone to methylation, while acetylation is associated only with histones. (
  • The first important advance was defining the enzymes governing acetylation, methylation, and phosphorylation events at histones. (
  • A convenient package of tools that allows the experimenter to measure global acetylation of histone H3 at tremendously fast speeds and consistency, superior and safer than all other current methods. (
  • The EpiQuik Global Histone H3 Acetylation Assay Kit is suitable for specifically measuring global histone H3 acetylation using a variety of mammalian cells including fresh and frozen tissues, and cultured adherent and suspension cells. (
  • By altering the acetylation status of an array of substrates, including histones, transcription factors, and chaperone proteins, HDAC inhibitors (HDACi) reprogram the cellular machinery to induce such processes as cell cycle arrest, differentiation, and apoptosis ( 1 - 3 ). (
  • Neuronal activity-induced expression of Arc (1) increases endogenous nuclear Tip60 puncta, (2) recruits Tip60 to PML bodies, and (3) increases histone acetylation of Tip60 substrate H4K12, a learning-induced chromatin modification. (
  • We present data showing that Arc associates with and enhances Tip60's acetylation of its substrate H4K12, an important learning-induced histone mark. (
  • Histone modifications, such as methylation and acetylation, or incorporation of histone variants can alter nucleosomal dynamics. (
  • Histone acetylation, histone methylation, and DNA methylation modifiers are each further stratified into "writers" (w), "editors" (e), and "readers" (r). (
  • Researchers from the University of California, Santa Cruz and Indiana University, Bloomington, found that although the tags in each chromosome are reduced as a result of division, subsequent recruitment of histone-modifying enzymes reestablishes the full tag quota, thus preserving the memory of modifications for the next round of division. (
  • Although the presence of these modifications at given genomic locations can be inherited from a parent cell to its daughters, exactly how this landscape of histone modifications is reestablished after DNA replication-when the histones are temporarily evicted from DNA-was unclear. (
  • There's been a lot of debate about whether histone modifications can be heritable," said Bill Kelly , a biologist at Emory University in Atlanta, Georgia, who was not involved in the study. (
  • One theory suggests "histone modifications on the original mother chromosome get split between the two daughter chromosomes and probably diluted," she said. (
  • An opposing theory, however, suggests "histone modifications are not passed through DNA replication. (
  • But, importantly, what the researchers could see was that, "histone modifications are indeed passed to the daughter chromosomes-the chromosomes derived from the initial sperm chromosomes-and the oocyte chromosomes, which did not have the mark to begin with, do not acquire it," she added. (
  • An extra scoop of ice cream, coffee and a cake, or the epigenetic delights of single-cell profiling of not one but two histone modifications? (
  • In their latest, the team doubled down on sortChIC-seq to develop scChIX-seq, which doubles your epigenetic fun by deciphering the single-cell interplay of multiple histone modifications. (
  • The service involves testing prostate cancer biopsies or FFPE/frozen tissue samples obtained from patients who have previously undergone radical prostatectomy or other treatments to assess the level of aggressiveness of disease and chance of recurrence through analysis of global histone modifications. (
  • The researchers looked at 42 different combinations of modifications on peptides from the histone 3 protein across 115 cancer cell lines. (
  • And, upon examining the other seven lines, the researchers discovered in these lines a previously unknown NSD2 variant that, likewise, was linked to the cluster's characteristic histone modifications. (
  • Longitudinally tracking changes in the histone modifications, on the other hand, could provide a measure of a treatment's effectiveness. (
  • To achieve this, the researchers reconstruct known chemical histone modifications in a test tube and investigate which proteins selectively bind to them in an extract made from the nuclei of cells. (
  • Here, I present EPIGENE, a novel chromatin segmentation method for identifying genome-wide active TUs using transcription-associated histone modifications. (
  • Unlike existing chromatin segmentation approaches, EPIGENE uses a constrained, semi-supervised multivariate Hidden Markov Model (HMM) that models the observed combination of histone modifications using a product of independent Bernoulli random variables to identify the chromatin state sequence underlying an active TU. (
  • Epigenetic modifications include DNA methylation, histone modification and noncoding RNA expression [ 2 ]. (
  • Histone modifications induce changes of chromatin structure and thereby affect the accessibility of transcription factors, nuclear proteins and enzymes to genomic DNA, resulting in gene activation or repression. (
  • It is known that histone modifications play critical roles in DNA repair, DNA replication, transcription regulation, alternative splicing and chromosome condensation and some diseases including autoimmune diseases and cancers. (
  • How Do Histone Modifications Regulate Gene Expression? (
  • Modifications in the core regions of the histones had remained unknown until recently. (
  • The ability of eukaryotic cells to maintain distinct phenotype, although containing identical genetic constituents is ensured by various chemical modifications occurring on DNA and histones. (
  • These enzymes and protein domains carry out most of the epigenetic modifications on DNA and histone tails. (
  • Modifications of DNA and histone proteins occur through the addition of various chemical groups utilizing numerous enzymes. (
  • And, third is discovering histone modifications not only alter the interactions they have with DNA, but also act as ligands for binding of other proteins. (
  • Taking advantage of technologies used by our friends in proteomics, researchers at Princeton University explored the turnover of various histone proteins and how post-translational modifications (PTMs) alter the speed of that process. (
  • Histone modifications play a critical role in coordinating accurate gene expression. (
  • The functional roles of specific histonemarks has informed the basis of our understanding for underlying mechanisms of leukemia, while globalanalyses of interacting histone modifications has begun to distinguish subtypes of leukemia with prognosticand therapeutic implications. (
  • In this current era of personalized and precision medicine, it will be necessary tonot only identify the specific genetic mutations present in a patient's leukemia but to also appreciate thedynamic chromatin states which are driven by histone modifications that can aid our diagnostic and therapeuticstrategies for improved management of leukemia. (
  • Methods: To investigate the differences of histone H3 modifications involved in transcription, we determined the genome-wide profiles of H3K4me3, H3K27ac, and H3K27me3 in brain cortexes of an Alzheimer mouse model (PSAPP). (
  • The analysis of transcription starting sites (TSS) signal distribution, and analysis of bounding sites revealed that gastrocnemius is more influenced than brain by sex for the three histone modifications considered, exception made for H3K27me3 distribution on the X chromosome which showed sex-related differences in promoters belonging to behavior and cellular or neuronal spheres in mice cortexes. (
  • While HDAC inhibitors administered at hyper-acute time points are an important therapeutic option, reports of long-lasting histone hypoacetylation due to HDAC and histone acetyltransferase dysfunction after stroke ( Park and Sohrabji, 2016 ) indicate the possible effectiveness of HDAC inhibitors at acute (1-7 d) time points as well. (
  • uncover that the viral ORF8 protein mimics the H3 histone protein to disrupt epigenetic regulation. (
  • Going fishing in the protein pond using histones as a bait - how do cells decide how to repair their DNA? (
  • Western Blot: Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) [NBP1-30141] - Representative Western blot showing M-track protein protein proximity signals obtained for Kic1. (
  • Furthermore, our analysis revealed that histone deacetylase 14 (HDA14) is the first organellar-localized RPD3/HDA1 class protein found to reside in the chloroplasts and that the majority of its protein targets have functions in photosynthesis. (
  • Each histone protein is known to have several variants based on amino acid substitutions. (
  • Histone H3K27 trimethylation (H3K27me3) has been linked to polycomb-group-protein-mediated suppression of Hox genes and animal body patterning, X-chromosome inactivation and possibly maintenance of embryonic stem cell (ESC) identity. (
  • Genomic DNA is wrapped around a protein octamer which contains four core histones (H2A, H2B, H3, H4), forming the structure of the nucleosome [ 9 - 11 ]. (
  • This monoclonal antibody was raised against a peptide sequence derived from the C-terminal domain of human Histone H3 protein. (
  • Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. (
  • Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. (
  • Upon analysis of differential expression for the sets of phosphonull and phosphomimetic mutants, they showed the proteins most affected by histone methylation clustered into GO categories consistent with cellular response to stress, e.g. ion membrane transport, lipid biosynthesis, ergosterol biosynthesis, and protein mannosylation. (
  • The hyperthermophilic archaeon Methanothermus fervidus contains two small basic proteins, HMfA (68 amino acid residues) and HMfB (69 residues) that share a common ancestry with the eukaryal nucleosome core histones H2A, H2B, H3, and H4. (
  • Histones are a group of similar, small, highly conserved nuclear proteins that bind to DNA by their many basic residues. (
  • Histone methylation usually occurs on the N-terminal histone tail of lysine (K) and arginine (R) residues [ 8 ]. (
  • The histone proteins have tails that project from the nucleosome and many residues in these tails can be post-translationally modified, influencing chromatin compaction and transcription. (
  • writers - a host of enzymes capable of modifying nucleotide base and specific amino acid residues on histones, erasers - a group of enzymes proficient in removing these marks, and readers - a diverse range of proteins that possess specialized domains recognizing specific epigenetic marks in a locus. (
  • Methylation of histones is a unique post-translational modification since it can add up to three methyl groups on the single lysine (K) residues resulting in mono (me1), di (me2) and tri-methylated (me3) states. (
  • Using AlphaFold , they modeled the relationship between the specific phosphorylated residues and showed the key regulator of methylation activity ( T127 on Set2p) is spatially proximal to the target lysine residue in the histone. (
  • two asterisks (**) denote the histone-modifying genes without assignment of residues in the histone tails. (
  • Histone H3 peptide tri-methylated at Lysine 9, biotinylated, substrate for histone demethylases belonging to the Jumanji domain-containing (JMJ) family. (
  • The recent discovery of a large number of histone demethylases suggests a central role for these enzymes in regulating histone methylation dynamics. (
  • However, comprehensive understanding of the expression profiles of histone methyltransferases and demethylases in lung cancer is still lacking. (
  • The mutation, expression level, association with survival and clinical parameters of histone methyltransferases and demethylases were determined. (
  • We summarize recent data that indicate a close relationship between GC density of promoter sequences, transcription factor binding and the antagonizing activities of distinct epigenetic regulators such as histone methyltransferases (HMTs) and histone demethylases (HDMs). (
  • By adding a small molecule called an acetyl group to histones, histone acetyltransferases control the activity of certain genes. (
  • Scientists show how roundworm daughter cells remember the histone modification patterns of their parents. (
  • There have been two theories as to how histone modification patterns might be remembered, said Santa Cruz's Susan Strome , the professor of molecular, cell, and developmental biology who led the new study. (
  • The authors found that, during infection, ORF8 associates with chromatin, disrupts the post-translational modification of histones and promotes chromatin compaction. (
  • The dynamic duo of Jake Yeung and Alexander van Oudenaarden (Hubrecht Institute-KNAW, the Netherlands) have been working double-time to move past specific technological barriers and develop advanced histone modification profiling techniques. (
  • A recent histone modification study led by Broad Institute researchers demonstrates the potential of high-resolution mass spectrometry for targeted proteomics. (
  • In the case of the Nature Genetics study, the high-res approach was necessary for distinguishing between highly similar histone modification patterns, Jaffe told ProteoMonitor . (
  • Littleton, CO, September 21, 2011 --( )-- Today, Novus added a new Histone H3 [dimethyl Lys9/phospho Thr6] antibody to their growing line of EpiPlusTM histone modification antibodies. (
  • Although dimethyl K9, phospho-T6 histone H3 is known to exist, very little comprehensive information about the importance of this modification and its mechanism has been published. (
  • This problem can be alleviated by chromatin-based approaches due to a well-established correlation between transcription and histone modification. (
  • ABSTRACT During development, covalent modification of both, histones and DNA contribute to the specification and maintenance of cell identity. (
  • Epigenetics often involves modification to proteins - such as histones - that interact with DNA. (
  • According to Kelly, the results suggest "that after replication there is sufficient information there that it can be targeted by the maintenance system"-the histone-modifying enzymes. (
  • However, the knowledge about the deacetylase functions is largely limited to histones, although these enzymes were found in diverse subcellular compartments. (
  • Writers, enzymes that add PTMs to histones, are divided into classes based on the specific PTM they effect. (
  • Similarly, erasers, enzymes which remove specific PTMs from histone substrates, are divided into PTM-specific classes. (
  • Dent's lab uses yeast and mouse models to understand the function of histone modifying enzymes. (
  • Sharon Dent, Ph.D., a leading scientist in the field of chromatin biology, may have had a sense of déjà vu on her recent visit to give a presentation on 'The Secret Lives of Histone Modifying Enzymes' at NIEHS Jan. 13. (
  • lab's research program focuses on understanding the function and regulation of histone modifying enzymes and their role in cancer and other diseases, an area which has seen explosive growth since the first histone acetyltransferases were discovered in 1996. (
  • Dent's group also uses mouse models to study the function of histone modifying enzymes. (
  • SUV39H is a typical histone methyltransferase involved in H3K9 trimethylation and promotes gene silencing. (
  • Histone lysine methyltransferase (KMTs) catalyzes the transfer of methyl group from AdoMet, producing three methylated products, and adenosylhomocysteine. (
  • One-well established function for the Set1 methyltransferase is to methylate the lysine 4 residue of histone H3. (
  • However, the functions of each histone variant are still unclear because of the diverse nature of histone variants. (
  • In the present study, they have shown for the first time that H3mm7, one of the histone variants, is substantially expressed in muscle stem cells. (
  • This study suggests that histone variants might be another vital factor as gene expression switches in determining unique expression profiles for specific tissues. (
  • Short H2A histone variants are expressed in cancer. (
  • Many of the XY deregulated genes are good candidates (such as histone variants) to explain these anomalies. (
  • The epigenetic writers are DNA methyltransferases, histone lysine methyltransferases and histone acetyltransferases. (
  • A class of proteins important for epigenetic regulation, histone methyltransferases (HMTs), plays multiple important roles in certain cancers. (
  • A study in worms published today (September 18) in Science reveals that part of the mechanism involves divvying up modified histones-molecular tags that label active or repressed genes-between daughter chromosomes at replication. (
  • In the past, many researchers believed that histones played a passive role in chromosome architecture and little role in specifically switching genes on and off. (
  • Moreover, evidence suggests that defects in the establishment of proper chromosome structure by histones may activate or silence genes aberrantly and thus lead to disease. (
  • They found that "silent" regions of chromosomes-where genes are kept "off" and DNA resists genetic recombination-contain one variety of histone H3. (
  • In contrast, the researchers found that "active" regions of chromosomes-where genes can be easily switched "on" and DNA can readily recombine-contain a slightly different variety of histone H3. (
  • In 2015, the research group of Professor Yasuyuki Ohkawa has reported novel mouse H3 variant genes which encoded highly conserved amino acid sequences compared to well-known histones. (
  • Additional experiments revealed that histone H3mm7 has a function to accelerate the gene expression level of muscle-related genes by relaxing the DNA structure in muscle stem cells. (
  • Histone methylation was reported to regulate the expression of a variety of genes in cancer. (
  • Mutation and copy number alteration of histone methylation related genes both exist in NSCLC. (
  • The expression of certain histone methylation related genes were significantly associated with overall survival and clinical attributes. (
  • Some histone methylation related genes might serve as potential prognosis predictor or therapeutic target for NSCLC. (
  • The significance of some histone methylation related genes was contrary to the literature and awaits further validation. (
  • Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a-induced H3K9me2 of histones, and for NL-LAD interaction. (
  • Chemical groups can be added or removed from histones to make the histones more tightly or loosely packed, turning genes "off" or "on. (
  • Non-coding RNA may also recruit proteins to modify histones to turn genes "on" or "off. (
  • Using the nematode Caenorhabditis elegans they show that the inheritance of small RNAs antisense to histone genes adversely affect the fertility of worms across generations until they become sterile. (
  • 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. (
  • In addition, they have demonstrated that the transmission of a pool of small RNAs antisense to histone genes into wild-type worms epigenetically affects their fertility. (
  • Finally, they have dissected the molecular mechanism by which small RNAs antisense to histone genes are generated and transmitted across generations in piRNA mutants. (
  • Expresión de genes de histonas en Trypanosoma cruzi : caracterización de histonas / por Gabriela Cecelia Toro Acuña. (
  • Core histones are predominantly globular except for the unstructured N-terminal tails. (
  • Aside from geneticmutations which cause altered DNA sequence, it has become increasingly clear that aberrant post-translationalmodifications of histone tails are also associated with leukemogenesis. (
  • Bromodomains (BRDs) are small regions found in a variety of proteins that recognize and bind acetylated histone tails. (
  • Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetylated histone tails, have shown therapeutic promise in several diseases. (
  • Core histones form an octamer, which contains two H2A-H2B dimers and one H3-H4 tetramer. (
  • The relatively new therapeutic option with the use of histone deacetylase inhibitors is being advanced in the hope of decreasing morbidity and mortality associated with the disease. (
  • Histone deacetylase inhibitors have been shown to induce changes in gene expression, affecting cell cycle regulation, differentiation, and apoptosis. (
  • 2004. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. . (
  • Nucleosomes are formed by 150-210 base pairs (bp) of double stranded (ds) DNA and an octamer of highly conserved histone proteins. (
  • Methods: One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139, yielding a focal product (g-H2AX) that can be detected by a fluorescent antibody. (
  • EpiQuik Global Histone H3-K4 Methylation Assay Kit. (
  • These phenotypic observations led Dent to conclude, 'Gcn5 functions early in development, but independent of its histone acetyltransferase activity. (
  • Metastasis-associated (MTA) family proteins are components of the histone deacetylase and nucleosome remodelling complex (NuRD). (
  • a Stacked bar chart demonstrating the global PTMs identified for Histone H3.3. (
  • SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry. (
  • Histone H3 in silent DNA had a "methyl" group attached to a particular lysine amino acid, #9. (
  • The histones are divided into fractions, with each fraction having a distinct amino acid composition and sequence. (
  • This Histone H3 [Trimethyl Lys9] antibody (6F12-H4) was raised against a synthetic peptide made to an N-terminal region of Histone H3 (between amino acids 1-50). (
  • We report here a novel interaction between Arc and Tip60, a histone-acetyltransferase and subunit of a chromatin-remodelling complex, using biochemistry and super-resolution microscopy in primary rat hippocampal neurons. (
  • We now report that Arc interacts with the histone acetyltransferase Tip60, a subunit of the NuA4 chromatin modifying complex that functions in transcriptional regulation, implicated in Alzheimer's disease. (
  • Remodelers are multi-subunit complexes characterized by a conserved core ATPase responsible for breaking histone-DNA contacts. (
  • and de novo synthesized histones don't have marks put there by transcription or repression," he explained. (
  • Here, we found that HNRNPK can partially epigenetically regulate cancer cell proliferation via increasing transcription and exon 4-inclusion of SPIN1, an important oncogenic histone code reader. (
  • Eukaryotic DNA is packaged and wrapped around proteins known as histones which protect and regulate gene expression. (
  • The signal region is contained within the intron of JMJD1C , a histone demethylase that a recent study has found to regulate abnormal metabolic processes in AML(15). (
  • In the August 10 issue of Science, Cold Spring Harbor Laboratory researcher Shiv Grewal and his colleagues report that seemingly small differences between two varieties of histone have dramatic effects on chromosome structure and gene expression. (
  • Her team generated Caenorhabditis elegans eggs that lacked an enzyme called Polycomb repressive complex 2 (PRC2), a histone-modifying enzyme that methylates lysine 27 of histone H3 (H3K27me)-a mark associated with transcriptional repression. (
  • Usually exposed in the necrotic core of solid malignant tumors, the universal intracellular antigen (i.e., histone H1 complexed deoxyribonucleic acid) is an abundant, insoluble target for 131 I-chTNT-1/B mAb (Cotara®, Peregrine Pharmaceuticals, CA, USA). (
  • David Allis (University of Virginia), Grewal's colleague in this and another study published earlier this year in Science, has proposed that in addition to the now familiar genetic code of repeating As, Cs, Gs, and Ts in the sequence of DNA, a "histone code" exists in which differentially modified histone proteins can organize the genome into active and silent regions that can be stably inherited. (
  • Until recently, proteins called "histones" have been the Rodney Dangerfields ("I don't get no respect! (
  • DNA wraps around proteins called histones. (
  • We found overall upregulation of histone regulators in NSCLC. (
  • This comprises 426 ERGs classified into the main categories: histone modifiers, chromatin remodellers, and DNA methylation regulators. (
  • Put simply, we build a molecular bait with defined histones and use it to go fishing in the nucleus - and then it gets exciting to see what we will have on our 'hook'," says Bartke. (
  • Sodium phenylbutyrate is a histone deacetylase inhibitor shown to upregulate heat-shock proteins and act as a small molecular chaperone, thereby ameliorating toxicity from endoplasmic reticulum stress. (
  • The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (yH2AX) as a short-term biomarker of DNA damage among roofers. (
  • Histone deposition pathways determine the chromatin landscapes of H3.1 and H3.3 K27M oncohistones. (
  • At gene promoters, this multi-layered regulation gives rise to a nucleosome-depleted region (NDR) flanked by positionally stable nucleosomes enriched in the histone variant H2A.Z. Due to their role in establishing and maintaining this stereotypical promoter chromatin structure, remodelers have been a topic of intense research in the past two decades. (
  • Whereas in old chromatin the lysine in position 20 of histone H4 (H4K20) is almost always modified with two methyl groups (H4K20me2), the chromatin that is newly formed during DNA synthesis is characterized by (still) no methyl groups being present at this position (H4K20me0). (
  • The mutations that cause the SBBYS variant of Ohdo syndrome likely prevent the production of functional histone acetyltransferase from one copy of the KAT6B gene in each cell. (
  • A fifth variant (FAM71A rs147978008) showed nonrisk allele preferential binding to H1 histones. (
  • As prolines are present at these positions in all archaeal histone sequences, this proline-tetrad structure is likely to be a common feature of all archaeal histone dimers. (
  • Histones are proteins around which our DNA is wrapped and which thus serve to package the genetic material," says corresponding author Dr. Till Bartke, deputy director of the Institute of Functional Epigenetics (IFE) at Helmholtz Zentrum München. (
  • There are five lysines in histone H3 (K4, K9, K27, K36, K79) that have been shown to be modulated by methylation. (
  • Histone proteins are major determinants of gene regulation, and histone mimicry allows viruses to gain control of gene regulatory functions to support viral replication or suppress host antiviral responses. (
  • This finding was one of the first reports demonstrating cross-regulation on non-histone proteins. (
  • Regulation of histone methylation by automethylation of PRC2. (
  • Histones bind to DNA and wrap the genetic material into "beads on a string" in which DNA (the string) is wrapped around small blobs of histones (the beads) at regular intervals. (
  • Histone proteins H3 and H4 bind to form a H3-H4 dimer, two of these H3-H4 dimers combine to form a tetramer. (
  • Over the past several months, Novus has collaborated with 21st Century Biochemicals, a leading manufacturer of custom antibodies and peptides, to generate the most well validated antibodies for modified histones and other epigenetic targets. (
  • The new Histone H3 [dimethyl Lys9/phospho Thr6] Antibody (NB21-1053) has been validated for Western blot, ChIP, dot blot, and immunofluorescent staining on human, mouse and rat cell cultures. (
  • Chromatin Immunoprecipitation: Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) [NBP1-30141] - Used to perform ChIP on HeLa cells. (
  • Western Blot: Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) [NBP1-30141] - H3K9Me3 analysis of MCF7 and HCT116. (
  • Western Blot: Histone H3 [Trimethyl Lys9] Antibody (6F12-H4) [NBP1-30141] - Analysis of Histone H3 K9-me3 in HeLa histone lysates. (
  • Our result suggests that alteration of histone methylation is strongly involved in NSCLC. (
  • Our structures explain how the central domain of CENP-C achieves its high specificity for CENP-A nucleosomes and how CENP-C and CENP-N sandwich the histone H4 tail. (
  • Her work on the histone acetyltransferase Gcn5 demonstrated its involvement in mammalian development. (
  • Now, scientists who remained true to histone research are basking in the glow of renewed respect for the dynamic role that these proteins are being found to play in the inheritance of specialized chromosome structures and the control of gene activity. (
  • The new study in Science is one of several that are beginning to elucidate the role of histones and other proteins in such a chromosome replication process. (