The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.
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.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
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.
Databases devoted to knowledge about specific genes and gene products.
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.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
Studies beyond the bachelor's degree at an institution having graduate programs for the purpose of preparing for entrance into a specific field, and obtaining a higher degree.
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.
The part of the face that is below the eye and to the side of the nose and mouth.
Lining of the ORAL CAVITY, including mucosa on the GUMS; the PALATE; the LIP; the CHEEK; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous EPITHELIUM covering muscle, bone, or glands but can show varying degree of keratinization at specific locations.
The fixed oil obtained from the dried ripe seed of linseed, Linum usitatissimum (L. Linaceae). It is used as an emollient in liniments, pastes, and medicinal soaps, and in veterinary medicine as a laxative. It is also called flaxseed oil. (Dorland, 28th ed)
Viral proteins that are components of the mature assembled VIRUS PARTICLES. They may include nucleocapsid core proteins (gag proteins), enzymes packaged within the virus particle (pol proteins), and membrane components (env proteins). These do not include the proteins encoded in the VIRAL GENOME that are produced in infected cells but which are not packaged in the mature virus particle,i.e. the so called non-structural proteins (VIRAL NONSTRUCTURAL PROTEINS).
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
The procedures involved in combining separately developed modules, components, or subsystems so that they work together as a complete system. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Activities concerned with governmental policies, functions, etc.
The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. (Stedman, 25th ed)
The interchange of goods or commodities, especially on a large scale, between different countries or between populations within the same country. It includes trade (the buying, selling, or exchanging of commodities, whether wholesale or retail) and business (the purchase and sale of goods to make a profit). (From Random House Unabridged Dictionary, 2d ed, p411, p2005 & p283)
The level of governmental organization and function at the national or country-wide level.
Materials or phenomena which can provide energy directly or via conversion.
A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.
Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

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 ...
... of histones[edit]. Eukaryotic DNA is organized with histone proteins in specific complexes called chromatin. ... Post-translational modification of histones such as histone phosphorylation has been shown to modify the chromatin structure by ... Molecular mechanisms of histone modification function. 1839 (8): 711-718. doi:10.1016/j.bbagrm.2014.04.013. PMC 4103482. PMID ... It was shown that MSK1 phosphorylated histone H2A on serine 1, and mutation of serine 1 to alanine blocked the inhibition of ...
Histones are absent. However, recent EST sequencing has revealed the presence of histones in one of the closest relative to ... However, histone-like proteins of bacterial origins are found in the coding regions at periphery of the dinokaryon's ...
In mammals, key architectural proteins include: Histones: DNA is wrapped around histones to form nucleosomes, which are basic ... B compartments, on the other hand, tend to be gene-poor, compact, contain histone markers for gene silencing, and lie on the ... In order for DNA to pack inside the tiny cell nucleus, each strand is wrapped around histones, forming nucleosome structures. ... Each nucleosome consists of 8 histone protein subunits, around which roughly 147 DNA base pairs are wrapped in 1.67 left-handed ...
... such as lack of histones, have supported this division, although some crenarchaea were found to have histones. Until recently ... ISBN 978-0-13-144329-7. Cubonova L, Sandman K, Hallam SJ, Delong EF, Reeve JN (2005). "Histones in Crenarchaea". Journal of ...
The histone variant H2AX constitutes about 10% of the H2A histones in human chromatin. γH2AX (H2AX phosphorylated on serine 139 ... In addition to core histones, a linker histone H1 exists that contacts the exit/entry of the DNA strand on the nucleosome. The ... histone modification). Most modifications occur on histone tails. The consequences in terms of chromatin accessibility and ... The histones are mostly displaced, and replaced by protamines (small, arginine-rich proteins). It is proposed that in yeast, ...
In eukaryotic cells, DNA is associated with about an equal mass of histone proteins in a highly condensed nucleoprotein complex ... Protamines replace histones during spermatogenesis. The most widespread deoxyribonucleoproteins are nucleosomes, in which the ... The prototypical examples are nucleosomes, complexes in which genomic DNA is wrapped around clusters of eight histone proteins ... The proteins combined with DNA are histones and protamines; the resulting nucleoproteins are located in chromosomes. Thus, the ...
Rudolph, Johannes; Luger, Karolin (2020-07-03). "The secret life of histones". Science. 369 (6499): 33. Bibcode:2020Sci...369 ...
Her studies of histones with Mirsky provided evidence for lysine-rich histones, in contrast to the arginine-rich histones ... She studied histones, proteins found in cell nuclei, and was able to show the amino acid composition of various histone ... Histones have since been shown to be important in gene expression. Daly's work on histones is now considered fundamental. Daly ... Brusch, Harris (1965). Histones and other nuclear proteins. Academic Press. pp. 13-15, 76-77. ISBN 9780123955937. Retrieved 8 ...
She received her Ph.D. from NYU in 1964; her thesis was on histones. Skalka joined the Phage group at the Cold Spring Harbor ...
... which is a histone modification that has been characterized as part of the histone code. The histone code is the theory that ... As a histone methyltransferase (HMTase), EZH2's primary function is to methylate Lys-27 on histone 3 (H3K27me) by transferring ... Recent work has shown that at least part of the silencing function of the EZH2 complex is the methylation of histone H3 on ... Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y (2002). "Role of histone H3 lysine 27 ...
In general, histone methylation leads to gene repression but gene activation can also be achieved. Evidence has shown histone ... In eukaryotic cells, DNA is tightly packed by histones. Modification on histones can change interactions with DNA which can ... Whetstine JR (2010). "Histone Methylation". Handbook of Cell Signaling (Second ed.). pp. 2389-2397. doi:10.1016/b978-0-12- ... Epigenetic regulations such as DNA methylation and histone methylation can repress gene expression by inhibiting initiation of ...
Histone post-translational modifications modify the chromatin structure. The most commonly associated histone phosphorylation ... Post-translational modification of histones such as histone phosphorylation has been shown to modify the chromatin structure by ... It was shown that MSK1 phosphorylated histone H2A on serine 1, and mutation of serine 1 to alanine blocked the inhibition of ... Molecular mechanisms of histone modification function. 1839 (8): 711-718. doi:10.1016/j.bbagrm.2014.04.013. PMC 4103482. PMID ...
Anti-histone Histones 60[62]. 90[62]. -[62]. -[62]. -[62]. -. -[62] Anti Scl-70 Type I topoisomerase -[62]. -[62]. 20[62]. 10[ ... Anti-histone antibodies[edit]. Anti-histone antibodies are found in the serum of up to 75-95% of people with drug induced lupus ... Procainamide causes a form of drug-induced lupus that produces antibodies to the histone H2A and H2B complex.[39][40] ... This pattern is associated with anti-dsDNA antibodies, antibodies to nucleosomal components, and anti-histone antibodies. There ...
The phylum "Heimdallarchaeota" was found to have N-terminal core histone tails, a feature previously thought to be exclusively ... Henneman B, van Emmerik C, van Ingen H, Dame RT (September 2018). "Structure and function of archaeal histones". PLOS Genetics ...
... such as histone deacetylases and other chromatin remodeling proteins that can modify histones, thereby forming compact, ... Methylation talk between histones and DNA". Science's Compass. Science. 294 (5549): 2113-5. doi:10.1126/science.1066726. hdl: ... In yeast at least, H3K36me3 recruits enzymes such as histone deacetylases to condense chromatin and prevent the activation of ... "Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription ...
In 1884, Albrecht Kossel discovered histones. In 1888, Sutton and Boveri proposed the theory of continuity of chromatin during ...
Although certain histone modifications at centromeres seem to serve a purpose-for example, contributing to a higher order ... However, even though the CENPA histone variant is in fact conserved, there is a surprisingly large amount of diversity in the ... Specifically, in chicken DT40 cells, it was found that neither histone modifications nor early replication timing is associated ... Müller, Sebastian; Almouzni, Geneviève (2014-03-01). "A network of players in H3 histone variant deposition and maintenance at ...
These carry reduced number of histones. In place of histones, dinoflagellate nuclei contain a novel, dominant family of nuclear ... bind DNA with similar affinity to histones, and occur in multiple posttranslationally modified forms. Dinoflagellate nuclei ... as some of them lack histones and nucleosomes, and maintain continually condensed chromosomes during mitosis. The ...
Histones are removed during DNA replication; following behind the replisome, histones start to assemble as immature pre- ... Incorporation of alternative histones and post-translational modifications (PTMs) play an integral role in regulating the ... Drosophila dCHD1 can edit nucleosomes by swapping out histone H3 for the variant H3.3. Binding of dCHD1 near the nucleosome ... To relieve this tension, an upstream H3 dimer is displaced from the nucleosome, allowing for its replacement by histone variant ...
It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a ... Histone methylation Histone methyltransferase Blanc, Roméo S.; Richard, Stéphane (2017). "Arginine Methylation: The Coming of ... The post-translational modification of histone tails by either histone-modifying complexes or chromatin remodeling complexes is ... histone marks. The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as histones. The complexes ...
The carboxyl (C) terminal end of these histones contribute to histone-histone interactions, as well as histone-DNA interactions ... It is a mark that indicates the acetylation at the 9th lysine residue of the histone H3 protein. The H3K9 histone has two jobs ... In histone acetylation and deacetylation, histone proteins are acetylated and deacetylated on lysine residues in the N-terminal ... It is thought that a Histone code dictates the expression of genes by a complex interaction between the histones in a ...
... is a drug which acts as a histone deacetylase inhibitor, and was one of the first compounds discovered via high- ... Su GH, Sohn TA, Ryu B, Kern SE (June 2000). "A novel histone deacetylase inhibitor identified by high-throughput ... January 2013). "Scriptaid, a novel histone deacetylase inhibitor, protects against traumatic brain injury via modulation of ... Monneret C (January 2005). "Histone deacetylase inhibitors". European Journal of Medicinal Chemistry. 40 (1): 1-13. doi:10.1016 ...
This modification is found in many proteins, including histones. The potential role of succinylation is under investigation, ... "Lysine succinylation and lysine malonylation in histones". Molecular & Cellular Proteomics. 11 (5): 100-7. doi:10.1074/mcp. ...
The nucleosome comprises two copies of histone H3 and histone H4. These nucleosomes form a heterotetramer and bind to DNA in ... whereas co-repressors containing histone deacetylases confer transcriptional repression. Histones are locally modified on ... Since histone acetylation and the cAMP-PKA-CREB1 pathway are extremely important for normal hippocampal function and aging in ... Studies of the in- vivo composition of histone H3 complexes, as well as the structural of the ASF1-H3-H4 complex, have shown ...
The histone octamer is made of eight total histone proteins, two of each of the following proteins: H2A, H2B, H3, and H4. ... This is because the histone tail domains are involved in interactions between nucleosomes. The linker histone, or H1 protein, ... One portion of core histone proteins, known as histone tail domains, are extremely important for keeping the nucleosome tightly ... For instance, an enzyme writer can methylate Lysine-9 of the H3 core protein, which is found in the H3 histone tail domain. ...
To ensure this, histone chaperones disassemble the chromatin before it is replicated and replace the histones in the correct ... Double-stranded DNA is coiled around histones that play an important role in regulating gene expression so the replicated DNA ... "Chaperoning histones during DNA replication and repair". Cell. 140 (2): 183-195. doi:10.1016/j.cell.2010.01.004. PMC 3433953. ... must be coiled around histones at the same places as the original DNA. ...
Histone acetyltransferase KAT7 is an enzyme that in humans is encoded by the KAT7 gene. It specifically acetylates H4 histones ... "Entrez Gene: MYST2 MYST histone acetyltransferase 2". Sterner DE, Berger SL (Jun 2000). "Acetylation of histones and ... Cervoni N, Detich N, Seo SB, Chakravarti D, Szyf M (Jul 2002). "The oncoprotein Set/TAF-1beta, an inhibitor of histone ... Miotto B, Struhl K (Oct 2008). "HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1". Genes & ...
Histone H1.3 is a protein that in humans is encoded by the HIST1H1D gene. Histones are basic nuclear proteins responsible for ... "Isolation and characterization of two human H1 histone genes within clusters of core histone genes". Genomics. 10 (4): 940-8. ... The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher ... "Entrez Gene: HIST1H1D histone cluster 1, H1d". Allen BS, Stein JL, Stein GS, Ostrer H (1991). "Single-copy flanking sequences ...
The carboxyl (C) terminal end of these histones contribute to histone-histone interactions, as well as histone-DNA interactions ... In histone acetylation and deacetylation, histone proteins are acetylated and deacetylated on lysine residues in the N-terminal ... It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a ... The post-translational modification of histone tails by either histone modifying complexes or chromatin remodeling complexes ...
The carboxyl (C) terminal end of these histones contribute to histone-histone interactions, as well as histone-DNA interactions ... In histone acetylation and deacetylation, histone proteins are acetylated and deacetylated on lysine residues in the N-terminal ... Histone code Histone acetylation Sadoul K, Boyault C, Pabion M, Khochbin S (2008). "Regulation of protein turnover by ... It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a ...
histone cluster 1 H4 family member e. H4FJ. H4/j. 6p22.2. HIST1H4F histone cluster 1 H4 family member f. H4FC. H4/c, H4. 6p22.2 ... histone cluster 1 H3 family member b. H3FL. H3/l. 6p22.2. HIST1H3C histone cluster 1 H3 family member c. H3FC. H3/c, H3.1. ... histone cluster 1 H3 family member d. H3FB. H3/b. 6p22.2. HIST1H3E histone cluster 1 H3 family member e. H3FD. H3/d, H3.1. ... histone cluster 1 H3 family member g. H3FH. H3/h. 6p22.2. HIST1H3H histone cluster 1 H3 family member h. H3FK. H3/k, H3F1K. ...
Classes and histone variants[edit]. Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4.[2][4][5][6] Histones ... Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones.[12] Histone proteins are among the most ... Collectively, it is thought that histone modifications may underlie a histone code, whereby combinations of histone ... while histones H1/H5 are known as the linker histones. The core histones all exist as dimers, which are similar in that they ...
Histone-modifying enzymes. References[edit]. *^ Jenuwein T, Allis C (2001). "Translating the histone code". Science. 293 (5532 ... "Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification". Cell. 146 (6): 1016 ... Structural determinants of histone recognition by readers, writers and erasers of the histone code are revealed by a growing ... Many of the histone tail modifications correlate very well to chromatin structure and both histone modification state and ...
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 ... There are five families of histones which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The ... Collectively, it is thought that histone modifications may underlie a histone code, whereby combinations of histone ...
histone (hĬs´tōn), any of a class of protein [1] molecules found in the chromosomes of eukaryotic cells [2]. They complex with ... histone One of a group of basic, globular, simple proteins that have a high content of the amino acids arginine and lysine. ... histone One of a group of basic, globular, simple proteins that have a high content of the amino acids arginine and lysine. ... histone Any of a group of water-soluble proteins found in association with the DNA of plant and animal chromosomes. They ...
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 ...
DNA is wrapped around proteins called histones. These histones are crucial for efficient packaging of DNA, as well as the ... Due to their affiliation with DNA, histones are important for successful cell replication, which takes place via the cell cycle ... Each histone subtype has several copies of the same gene to allow for the large demand placed during DNA replication. Histones ... Methylation of histones does not usually change as much as phosphorylation does. Some methylation alterations of H3 histones ...
Among the well-known covalent modifications of histones, the reversible acetylation of internal lysine residues in histone ... Histone acetyltransferases.. Roth SY1, Denu JM, Allis CD.. Author information. 1. Department of Biochemistry and Molecular ... This review discusses our current understanding of histone acetyltransferases (HATs) or acetyltransferases (ATs): their ... multisubunit enzyme complexes responsible for bringing about the targeted acetylation of histones and other factors. ...
Location and function of linker histones.. Vignali M, Workman JL.. Abstract. The linker histones, H1 and its variant forms, ...
Only eukaryotes, with their millions and billions of base pairs have histones although there are homologs in some non-nuclear ... Since genes have to be unpacked to be read, the chromatin (histone-DNA) structure has to be dynamic to allow transcription ... Unsurprisingly, the sequence of the histone is very well conserved as it probably cannot tolerate much change to structure. DNA ... How the histones are packaged up into higher order complexes is largely unknown. ...
... data for nucleosomes containing linker histones. A recent cryo-EM study of histone H1 bound to nucleosomes (11) revealed that ... insights into the structure and function of linker histones within chromatin have emerged only recently (1). Linker histones ... Linker histones as liquid-like glue for chromatin. Eric B. Gibbs and Richard W. Kriwacki ... Linker histones play essential roles in chromatin structure and function by binding to nucleosomes and modulating the ...
Histone H2A (IPR002119). Short name: Histone_H2A Family relationships *Histone H2A (IPR002119) *Core histone macro-H2A ( ... Histone H2A is a small, highly conserved nuclear protein that, together with two molecules each of histones H2B, H3 and H4, ... In the mouse, histone H2A can be replaced by histone H2A-like 1 [PMID: 17261847]. ... Phylogenetic analysis of the core histones H2A, H2B, H3, and H4.. Nucleic Acids Res. 22 174-9 1994 ...
A nucleosome consists of a DNA left-handed double helix that is wrapped around core proteins called histones. Nucleosomes are ... There are two copies each of four histone proteins: Histone 2A, Histone 2B, Histone 3, and Histone 4. Histone 1 exists as a ... The tails of histone proteins stick out and are available to be modified by different histone modifying enzymes as signals for ... The strand of DNA winds around a histone octomer protein. Each nucleosome core particle is separated by about 80 base pairs of ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Obama softens his tone on offshoring. All thats missing is a plan for the H-1B visa. * ...
Histone definition, any of a group of five small basic proteins, occurring in the nucleus of eukaryotic cells, that organize ... histone. histology, histolysis, histoma, histometaplastic, histomorphology, histone, histone base, histonuria, ... Histones are also involved in controlling which sequences of DNA are turned on for transcription of RNA. When histones are ... histone. *. The histone was so toxic that its anaphylactic properties could not be studied. ...
They can loosely be separated into entities on the basis of their similarity to various yeast histone deacetylases. The first ... Since the identification of the first histone deacetylase (Taunton et al., Science 272, 408-411), several new members have been ... The human histone deacetylase family Exp Cell Res. 2001 Jan 15;262(2):75-83. doi: 10.1006/excr.2000.5080. ... The results obtained suggest that the number of histone deacetylases within the human genome may be as high as 17 and are ...
A histone antibody test detects these autoantibodies in the blood to help diagnose drug-induced lupus, ... Histone antibodies are proteins produced by the immune system that mistakenly target the bodys own tissues. ... The histone antibody test may be repeated at intervals after the drug has been discontinued to monitor for decreases in histone ... A positive histone antibody result by itself does not establish a diagnosis. About 50% of those with SLE will have histone ...
Histones undergo a wide range of post-translational modifications. These mainly occur in the amino-terminal tail of the histone ... Histones. Histones are small, simple proteins, usually occurring in the cell nucleus, that organize strands of DNA into ... Histone modification provides an epigenetic mechanism that enables a range of essential healthy and disease-related processes ... Histone post-translational modifications affect many chromatin-based reactions and those that influence gene expression are ...
Histone GO Peptides include sequences that are acetylated and di- or tri-methylated. For sequences that are ... Covalent modification on the amino terminal of the core histones through de/acetylation, de/methylation and de/phosphorylation ... the world s largest provider of on-demand GO peptides is pleased to announce the rapid expansion of our histone peptide ... The core histones (H2A, H2B, H3 and H4) act as spools around which DNA winds. ...
immunogen = KLH-conjugated, synthetic peptide corresponding to amino acids 118-126 (CG-AVTKYTSSK) of human Histone H2B ...
The available evidence suggests that H1 histones accept phosphate groups at different sites in response to different stimuli. ... The phosphorylation of H1 histones is reviewed. Consideration is given to phosphorylation reactions which occur in both ... Phosphorylation of H1 histones Mol Cell Biochem. 1983;57(1):81-92. doi: 10.1007/BF00223526. ... The phosphorylation of H1 histones which occurs during cell replication is reviewed in detail, and it is concluded that there ...
What you always wanted to know about histones. 12 Feb 2013 , 1:52 PM. , Posted by Nicole Rusk , Category: Genetics & Genomics, ... If you have wondered about the nature of the histone code, if you have questions about the importance of its writers, readers ... The fact is that core histone proteins that make up the nucloeosme can be modified by a range of post translational ... Nature Methods and Nature Biotechnology will host a live discussion on why histone modifications matter in health and disease. ...
specific for acetylated histone H4, 10 kDa; weakly cross-reacts with acetylated histone H2B from HeLa cells ... Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13): ... to a.a. 2-19 of Tetrahymena histone H4 (AGGAcKGGAcKGM GAcKVGAAcKRHS-C), acetylated on lysines 5, 8, 12 and 16 ...
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to map histone marks and transcription factor ... Figure 1: Rapid and robust analysis of histone marks and transcription factors by ChIPmentation.. ... ChIPmentation: fast, robust, low-input ChIP-seq for histones and transcription factors. *Christian Schmidl1. na1, ... Schmidl, C., Rendeiro, A., Sheffield, N. et al. ChIPmentation: fast, robust, low-input ChIP-seq for histones and transcription ...
The nucleosomes contain about 146 base pairs of DNA that are wound twice around a histone protein core. The histone proteins ... The amount of acetylation is controlled by two classes of enzymes, histone acetyl transferases ("HATs") and histone ... the inhibitor binds to the zinc atom and limits acetylation of the histone proteins. Accordingly, histone deacetylase ... P. A. Marks et al., Current Opinion in Oncology, 13: 477-483 (2001) describes histone deacetylase inhibitors as cancer drugs ...
In their Perspective, Cirillo and Zaret discuss new findings that highlight a fifth type of histone, the linker histone H1, ... Much chromatin research has centered on modifications to the core histones that regulate gene expression. ...
On the basis of machine learning, CEFCIG reveals unique histone codes for transcriptional regulation of reported CIGs, and ... to identify cell identity genes and master regulator transcription factors based on gene expression profiles and histone ... 1: CIGdiscover uncovers cell identity genes (CIGs) on the basis of the unique histone codes for their transcriptional ... Xia, B., Zhao, D., Wang, G. et al. Machine learning uncovers cell identity regulator by histone code. Nat Commun 11, 2696 (2020 ...
Enzymes such as histone acetyltransferases (HATs), histone methyltransferases (HMTs), histone deacetylases (HDACs) and histone ... HATs and HDACs are the two major enzyme classes involved in post-translational modification of N-terminal tail of the histone ... Histone Deacetylases (HDAC) Inhibitors Market, Players, trends and forecast 2016 - 2026. News provided by ... It presents an overview of the popularity of the keywords histone deacetylase inhibitor and HDAC inhibitor on Twitter and ...
Histone H3.3, an H3 variant that is found in all eukaryotes from yeast to human, is replication and cell cycle phase ... Two H2A/H2B heterodimers interact with an H3/H4 tetramer to form the histone octamer. It is also modified by various enzymes ... Histone H3 combines with Histone H4 to form the H3/H4 tetramer. ... Histone H3.3 Human, Recombinant Histone H3.3, an H3 variant ... Histones Products. Applications: Histones & Nucleosome Assembly. * Properties & Usage Storage Temperature. -20°C Storage ...
  • In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. (
  • The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. (
  • Histones are globular proteins with a flexible N-terminus (taken to be the tail) that protrudes from the nucleosome. (
  • The critical concept of the histone code hypothesis is that the histone modifications serve to recruit other proteins by specific recognition of the modified histone via protein domains specialized for such purposes, rather than through simply stabilizing or destabilizing the interaction between histone and the underlying DNA. (
  • histone Any of a group of water-soluble proteins found in association with the DNA of plant and animal chromosomes. (
  • histone One of a group of basic, globular , simple proteins that have a high content of the amino acids arginine and lysine . (
  • In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. (
  • In chromosomes, DNA is wrapped around proteins called histones. (
  • The S phase is characterized by DNA synthesis, and in the 1960s it was discovered that histone proteins are also synthesized during this phase. (
  • Transcriptional regulation in eukaryotes occurs within a chromatin setting and is strongly influenced by nucleosomal barriers imposed by histone proteins. (
  • Histone H2B is one of the 4 main histone proteins involved in the structure of chromatin in eukaryotic cells. (
  • Similar to other histone proteins, histone H2B has a distinct histone fold that is optimized for histone-histone as well as histone-DNA interactions. (
  • Hyperacetylation of histone tails helps DNA-binding proteins access chromatin by weakening histone-DNA and nucleosome-nucleosome interactions. (
  • These variants, also called isoforms, are proteins that are structurally very similar to the regular histone H2B but feature some specific variations in their amino acid sequence. (
  • Histone H2B isoforms interact differently with other proteins, are found in specific regions of chromatin, have different types and numbers of post-translational modifications, and are more or less stable than regular histone H2B. (
  • A nucleosome consists of a DNA left-handed double helix that is wrapped around core proteins called histones. (
  • The histone protein is composed of eight proteins. (
  • There are two copies each of four histone proteins: Histone 2A, Histone 2B, Histone 3, and Histone 4. (
  • The tails of histone proteins stick out and are available to be modified by different histone modifying enzymes as signals for transcription, replication, and DNA repair functions. (
  • DNA is normally conceived of as a spiral ladder, but in eukaryotic cells (cells with nuclei) the DNA in the nucleus is strung around a series of spool-shaped proteins known as histones. (
  • When histones are chemically modified in certain ways, they may loosen their hold on the DNA and allow it to become accessible to proteins that activate transcription, or they may tighten their hold on the DNA and make it inaccessible. (
  • The histones are among the most well-conserved proteins known. (
  • Histones are proteins that are a part of chromatin, the genetic material present in the nucleus of almost all cells within the body. (
  • Histones are small, simple proteins, usually occurring in the cell nucleus, that organize strands of DNA into nucleosomes. (
  • Therefore, the regulation of histone markers and the effect they have on the association of modification-specific binding proteins is an ongoing area of significant interest. (
  • The regulation of transcription in eukaryotes relies upon the histone proteins in several essential ways. (
  • The fact is that core histone proteins that make up the nucloeosme can be modified by a range of post translational modifications (current tally is 16) and that these PTMs, individually or collectively, send a message to the transcription machinery, either attracting or repelling it. (
  • Histone methyltransferases ( HMT ) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of histone proteins . (
  • Histones are basic proteins that confer order and structure to DNA and they play an important role in gene regulation. (
  • Are the histones fusion proteins or tagged proteins? (
  • The modified histone can be recognized by proteins containing a chromodomain, which preferentially binds H3K4me3. (
  • ING2, in turn, interacts with a larger histone deacetylase complex containing other associated proteins. (
  • These mechanisms are often mediated by histone linkers or by proteins associated with the recruitment of DNA-binding proteins, HDACI and II interacting proteins and transcriptional activators, coactivators or corepressors. (
  • Posttranslational modifications on histone proteins play a role in regulating chromatin structure and gene expression. (
  • This discovery centers on a specific type of histone, proteins that support DNA and help control its expression. (
  • Histones are proteins that act as spools to DNA's thread, giving the genetic code support, structure, and protection. (
  • Methyl-specific transcriptional repression requires chromatin assembly, and can be partially relieved by the histone deacetylase inhibitor Trichostatin A. In addition, several proteins have been identified that specifically bind to methylated DNA (6-8) . (
  • Conversely, the availability of histone proteins and their chaperones that help package the newly replicated DNA into chromatin in turn regulate replication fork progression. (
  • The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. (
  • The gene expression regulated by the chromatin, a densely packed complex structure containing DNA and histone proteins, has been found to be altered in patients of PD. (
  • These core histone proteins are subjected to posttranslational modifications on their N-terminal tails. (
  • However, how the WD40 repeat proteins facilitate enzymatic activities of histone modification enzymes is unclear. (
  • Histones undergo changes which alter their interaction with DNA and nuclear proteins. (
  • Histone proteins are among the most highly conserved proteins in eukaryotes, [14] which suggests they are vital to the biology of the nucleus. (
  • Core histones are highly conserved proteins, that is, there are very few differences among the amino acid sequences of the histone proteins of different species. (
  • Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. (
  • We favor the view that epigenetics, imposed at the level of DNA-packaging proteins (histones), is a critical feature of a genome-wide mechanism of information storage and retrieval that is only beginning to be understood. (
  • We review emerging evidence that histone proteins and their associated covalent modifications contribute to a mechanism that can alter chromatin structure, thereby leading to inherited differences in transcriptional "on-off" states or to the stable propagation of chromosomes by defining a specialized higher order structure at centromeres. (
  • HDACs remove acetyl groups from histones (and other nuclear proteins), inducing chromatin condensation and transcriptional repression. (
  • The only known role for Sir2 's catalytic activity in Saccharomyces cerevisiae silencing is to deacetylate N-terminal tails of histones H3 and H4, creating high-affinity binding sites for the Sir-protein complex, resulting in association of Sir proteins across the silenced domain. (
  • HDACs are a group of enzymes that remove functional acetyl groups from histone and non-histone proteins and they can affect cellular function through both epigenetic and non-epigenetic means. (
  • The study focused on histones, proteins that play a role in gene regulation. (
  • It has been well documented that the effects of histone acetylation and methylation on gene expression can be mediated by specific binding proteins called 'readers,'" Lee said. (
  • Recombinant proteins for H2A histone family member X are available from various sources. (
  • Your search returned 37 Proteins H2A histone family member X Recombinant Proteins across 12 suppliers. (
  • The modifications on the histone N-terminal tails are recognized by specialized proteins that selectively bind modified histones. (
  • Although the methylation of the terminal α-amino group has been found in H2B of a variety of organisms and a number of proteins other than histones. (
  • A postdoctoral position is available in the groups of Danica Fujimori and Mark Kelly in the Departments of Cellular and Molecular Pharmacology and Pharmaceutical Chemistry at UCSF (Mission Bay Campus) to investigate how the KDM5 family of histone demethylases regulate gene expression by modulating the methylation status of histone proteins within chromatin (Torres et al. (
  • Changes to chromatin, the structure that includes DNA and its associated histone proteins, is one key mechanism by which transcription is regulated ( Swygert and Peterson 2014 ). (
  • Histones are extensively decorated by covalent modifications that can affect chromatin compaction to influence transcription factor binding, or affect the recruitment of proteins that recognize specific histone modifications to activate or repress promoter activity ( Rothbart and Strahl 2014 ). (
  • The Jumonji C (JmjC) catalytic domain that demethylates histone H3 that is trimethylated at lysine 4 (H3K4me3) is the most characterized domain of KDM5 proteins ( Klose and Zhang 2007 ). (
  • In eukaryotic cells DNA is associated with histones and other proteins to form chromatin. (
  • Studies have also explored the analogous mechanism by which non-histone proteins may be enacted upon by both deacetylases and acetylases. (
  • Of all the proteins in eukaryotic cells, histones, first recognized in the late 1800s, are the proteins most frequently bound to DNA. (
  • Histones are small, highly conserved basic proteins. (
  • Nucleosomes consist of a histone octamer comprised of two copies of each of the core histone proteins H2A, H2B, H3, and H4, around which approximately 147 nucleotides of DNA is wrapped. (
  • The tumor suppressor CDC73 interacts with the ring finger proteins RNF20 and RNF40 and is required for the maintenance of histone 2B monoubiquitination. (
  • Schematic representation of the assembly of the core histones into the nucleosome. (
  • [8] The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place [9] and allowing the formation of higher order structure. (
  • Two copies of histone H2B come together with two copies each of histone H2A, histone H3, and histone H4 to form the octamer core of the nucleosome to give structure to DNA. (
  • Two of these heterodimers then bind together with a heterotetramer made of histone H3 and histone H4, giving the nucleosome its characteristic disk shape. (
  • Thus, while the structure and nucleosome-positioning role of the globular domain of linker histones are known, the structural details of CTD-linker DNA interactions have remained elusive. (
  • These mainly occur in the amino-terminal tail of the histone, which extends from the nucleosome surface. (
  • Moreover, nucleosome assembly is not necessarily repressive, since the folding of DNA by the histones can facilitate the activation of genes by bringing widely separated regulatory elements into juxtaposition. (
  • DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (
  • Regulation of chromatin in eukaryotic transcription requires histone-modifying enzymes, nucleosome remodeling complexes, and histone chaperones. (
  • Thoma, F., Koller, T. and Klug, A. (1979) Involvement of Histone H1 in the Organization of the Nucleosome and of the Salt-Dependent Superstructures of Chromatin. (
  • Lowary, P.T. and Widom, J. (1998) New DNA Sequence Rules for High Affinity Binding to Histone Octamer and Sequence-Directed Nucleosome Positioning. (
  • Tagami, H., Ray-Gallet, D., Almouzni, G. and Nakatani, Y. (2004) Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis. (
  • A ) Schematic representation of euchromatin and heterochromatin as accessible or condensed nucleosome fibers containing acetylated (Ac), phosphorylated (P), and methylated (Me) histone NH 2 -termini. (
  • Citation Query Histone variants, nucleosome assembly and epigenetic inheritance. (
  • Histone variants, nucleosome assembly and epigenetic inheritance. (
  • The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. (
  • The basic unit of chromatin is the nucleosome consisting of 140 bp of DNA wrapped around an octameric core of the four conserved histones H2A, H2B, H3 and H4. (
  • Nucleosome remodeling and histone modifications, mostly in histone tails, have been suggested to play a significant role in these processes ( Chen and Dent, 2014 ). (
  • Histone H1 distinguishes itself by falling outside of the core histone group, functioning to link strands of DNA on entry and exit of the nucleosome. (
  • Histone deacetylases are competating enzymes of HATs and are often associated with transcriptional repression and nucleosome condensation. (
  • While it is accepted that modifications (such as methylation , acetylation , ADP-ribosylation , ubiquitination , citrullination , and phosphorylation ) to histone tails alter chromatin structure, a complete understanding of the precise mechanisms by which these alterations to histone tails influence DNA-histone interactions remains elusive. (
  • [4] Methylation of histone lysine also has a role in DNA repair . (
  • Methylation of histones does not usually change as much as phosphorylation does. (
  • Some methylation alterations of H3 histones occur in the M phase, whereas many other H3s do not change noticeably. (
  • DNA looks much the same no matter what it codes for (although methylation makes a difference) and presumably wraps around the histone octamer in much the same way. (
  • Covalent modification on the amino terminal of the core histones through de/acetylation, de/methylation and de/phosphorylation affect chromatin structure and exquisitely regulate gene expression. (
  • The different epigenetic mechanisms through which gene expression can be modulated primarily include histone modification, DNA methylation, alteration of chromatin architecture and involvement of small-interfering or non-coding RNAs. (
  • [8] The level of chromatin compaction depends heavily on histone methylation and other post-translational modifications of histones [9] . (
  • Histone methylation is a principal epigenetic modification of chromatin [9] that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis. (
  • There are three different types of protein arginine methyltransferases (PRMTs) and three types of methylation that can occur at arginine residues on histone tails. (
  • In particular, triple methylation of lysine 4 of histone H3 (H3K4me3) is associated with all active genes. (
  • The interaction appears to be functionally important, because inhibition of histone modification (achieved by injection of Xenopus embryos with morpholino oligonucleotides to a factor required for the methylation) or depletion of BPTF caused similar developmental defects. (
  • In the last several years, oncogenomics applications have extended from identifying genes associated with cancer to analyzing transcript abundance in tumors (Transcriptome) [ 1 , 2 ], DNA methylation (Methylome) and histone acetylation (Acetylome) [ 3 , 4 ]. (
  • The transcriptome is highly influenced by histone modifications that are primarily driven by acetylation and methylation. (
  • They also found a global reduction in the levels of methylation of normal H3 histones when small amounts of the mutant H3 were added to normal human cells. (
  • The researchers went on to demonstrate that the reduction in methylation of normal H3 histones results from interference with activity of a methyltransferase called PRC2 by the mutant histone. (
  • We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. (
  • We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. (
  • Exciting research has shown that epigenetic changes in chromatin can affect gene transcription in response to environmental stimuli, and changes in key chromatin histone methylation patterns have been noted under diabetic conditions. (
  • Methylation at a specific lysine residue (K4) is involved in targeting histone tails for continuous acetylation and deacetylation. (
  • Histone modification including H3 lysine 79 methylation (H3K79me) plays a key role during gene transcription and DNA damage repair. (
  • or Kmt4) [4] or its mammalian homolog DOT1-Like (DOT1L) is the sole KMT in their respective genome with methylation activities toward H3K79 inside globular domain of histones. (
  • In addition to histone methylation, DOT1L can methylate other protein factors for regulation. (
  • The two modifications that influence each other do not have to reside on the same molecule as it has been demonstrated that the ubiquitination of H2B by Rad6 facilitates the methylation of H3K4, suggesting a crosstalk of the two histone tails. (
  • Epigenetic inheritance models posit that during Polycomb repression, Polycomb Repressive Complex 2 (PRC2) propagates histone H3K27 tri-methylation (H3K27me3) independently of DNA sequence. (
  • Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. (
  • Antibody Panel Packs for investigating histone modifications, including panels for histone H3 and H4 methylation, histone H3 and H4 acetylation, and histone H3 phosphorylation. (
  • Histone H3 Methylation Antibody Panel Pack I - Active Genes (H3K4m2, H3K4m3, H3K36m2, H3K36m3) incl. (
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  • Histone H3 Methylation Antibody Panel Pack I - Repression Genes (H3K9m2, H3K9m3, H3K27m2, H3K27m3) incl. (
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  • A diverse and elaborate array of post-translational modifications that include acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation, occur on the N-terminal tail domains of histones. (
  • Now you can easily purify histones and further separate the fractions of core histones from any cell culture or tissue sample while maintaining post-translational modifications like acetylation, methylation and phosphorylation. (
  • Reduction in uH2A reverses transcriptional repression and inhibits methylation of histone H3 at lysine 9 in cell culture. (
  • In contrast, reduction in uH2B induces transcriptional repression and inhibits methylation of histone H3 at lysine 4. (
  • Thus, histone monoubiquitylation is a potential bridge between histone acetylation and methylation, leading to changes in gene expression in HD. (
  • Submit your Twitter account related to Histone Methylation to be featured! (
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  • Disease and disorder research has been conducted in relation to the Histone Methylation Pathway and Malignant Neoplasms, Neoplasms, Cell Transformation, Neoplastic, Leukemia, Carcinogenesis. (
  • The study of the Histone Methylation Pathway has been mentioned in research publications which can be found using our bioinformatics tool below. (
  • The Histone Methylation Pathway has been researched in relation to Methylation, Dna Methylation, Demethylation, Histone Acetylation, Gene Silencing. (
  • The Histone Methylation Pathway complements our catalog of research reagents including antibodies and ELISA kits against HISTONE H3, HIST1H4F, HIST2H4A, KDM1A, POLYCOMB. (
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  • We have 454 products for the study of the Histone Methylation Pathway that can be applied to Western Blot, Chromatin Immunoprecipitation, Immunocytochemistry/Immunofluorescence, Flow Cytometry, Chromatin Immunoprecipitation (ChIP), Immunohistochemistry from our catalog of antibodies and ELISA kits. (
  • They can loosely be separated into entities on the basis of their similarity to various yeast histone deacetylases. (
  • However, due to the fact that several different research groups isolated the Hda1-like histone deacetylases independently, there have been various different nomenclatures used to describe the various members, which can lead to confusion in the interpretation of this family's functions and interactions. (
  • In the light of these recent discoveries, we have examined the literature data and conducted a database analysis of the isolated histone deacetylases and potential candidates. (
  • The results obtained suggest that the number of histone deacetylases within the human genome may be as high as 17 and are discussed in relation to their homology to the yeast histone deacetylases. (
  • Enzymes such as histone acetyltransferases (HATs), histone methyltransferases (HMTs), histone deacetylases (HDACs) and histone demethylases (DMTs) play significant role in epigenetic regulation. (
  • This pilot, three-week study will help scientists understand more about how the foods people eat can modify histone deacetylases, enzymes the body produces naturally. (
  • Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). (
  • 4 , 5 Histone acetylation/deacetylation balance, maintained dynamically by 2 important families of enzymes, histone acetyltransferases and histone deacetylases (HDAC), 6 controls the higher-order structure of chromatin and the resultant accessibility of transcriptional factors to their target genes. (
  • Two enzymes regulate these processes, histone deacetylases and histone acetyltransferases. (
  • Histone Deacetylases which is also commonly known as HDAC is best regarded as a class of enzymes. (
  • Histone Deacetylases has two main functions. (
  • Histone acetylation is a dynamic process whose levels are determined by the net activities of HATs and the competing enzymes histone deacetylases (HDACs). (
  • Histone deacetylases activities were often, but not always, associated with transcriptional repression and nucleosomal condensations. (
  • In animals, genes encoding canonical histones are typically clustered along the chromosome, lack introns and use a stem loop structure at the 3' end instead of a polyA tail. (
  • Genes encoding histone variants are usually not clustered, have introns and their mRNAs are regulated with polyA tails. (
  • The regulation of transcription of histone genes differs between eukaryotes. (
  • The replication independent histone genes are transcribed at a relatively constant low rate, regardless of cell cycle stage. (
  • However, most of the vertebrate histone genes are replication dependent and are therefore more highly expressed during the cell cycle's S phase. (
  • Given that the replication dependent histone genes all activate upon entry into the S phase, it is speculated that there exists some further upstream regulatory element. (
  • This mechanism is hypothesized to transduce a shared signal that activates the transcription of histone genes when the G1/S phase boundary is reached. (
  • Therefore, NPAT could be the link between cell cycle machinery and shared heightened transcription of histone genes during S phase. (
  • Specifically, in some lower eukaryotes, a histone H2B variant binds to a histone H2A variant called H2AZ, localizes to active genes, and supports transcription in those regions. (
  • Since genes have to be 'unpacked' to be read, the chromatin (histone-DNA) structure has to be dynamic to allow transcription machinery access. (
  • It is thought that the histones stay with the same sequences of DNA after cell replication, so the modifications of the histones and DNA allow the same sets of genes to be turned on and off in the daughter cells as in the parent cell. (
  • The genetic data demonstrate that the disruption of histone-DNA complexes plays a major role in the induction of transcription from many genes. (
  • Depending on the stage of the process, histone BigH1 is either present and represses specific genes or it is inhibited to allow gene expression, thereby promoting differentiation, a process in which stem cells produce adult sex cells. (
  • Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A," Nucleic Acids Research , vol. 34, no. 3, pp. 765-772, 2006. (
  • Histones and their modifications can play an important role in switching genes on and off -- a type of epigenetic control. (
  • Further, in senescent cells, the histone chaperone Hi stone R egulatory Homolog A (HIRA), a co-repressor of histone gene transcription, plays an important role in the formation of transcriptionally silent heterochromatin that incorporates replication-dependent histone genes as well as many genes needed for DNA replication to concomitantly shut down both histone and DNA synthesis. (
  • Role of transcriptional and posttranscriptional regulation in expression of histone genes in Saccharomyces cerevisiae. (
  • The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. (
  • The purpose of this study is to see if taking broccoli sprout extract alone, garlic oil alone, or broccoli sprout extract and garlic oil together, can decrease the action of histone deacetylase (HDAC) and turn on genes in white blood cells. (
  • This charge neutralization model has been challenged by recent studies, according to which transcriptionally active genes are correlated with rapid turnover of histone acetylation. (
  • We identified ZMYND8 as a reader for histone marks called H3K4me1 and H3K14ac, both of which are tied to metastasis-linked genes. (
  • The researchers also found that ZMYND8 worked with a histone modification "eraser" called JARID1D and successfully blocked metastasis-linked genes, they said in the statement. (
  • In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase. (
  • Mutations in histone H3 encoding genes occur in 80% of cases and portend a worse clinical prognosis. (
  • The human and mouse replication-dependent histone genes. (
  • Many of the histone tail modifications correlate very well to chromatin structure and both histone modification state and chromatin structure correlate well to gene expression levels. (
  • For details of gene expression regulation by histone modifications see table below . (
  • The hypothesis is that chromatin -DNA interactions are guided by combinations of histone modifications. (
  • Schematic representation of histone modifications. (
  • However, there are many more histone modifications, and sensitive mass spectrometry approaches have recently greatly expanded the catalog. (
  • Among the well-known covalent modifications of histones, the reversible acetylation of internal lysine residues in histone amino-terminal domains has long been positively linked to transcriptional activation. (
  • Histone H2B helps regulate chromatin structure and function through post-translational modifications and specialized histone variants. (
  • Acetylation and ubiquitination are examples of two post-translational modifications that affect the function of histone H2B in particular ways. (
  • Histone H2B is modified by a combination of several types of post-translational modifications. (
  • Histones undergo a wide range of post-translational modifications. (
  • Among the various types of epigenetic modifications, histone modification is of significant interest to researchers who want to understand the regulation of epigenetic and gene expression in different types of cells, cellular stages and cellular environments. (
  • Histone post-translational modifications affect many chromatin-based reactions and those that influence gene expression are particularly important since they can affect entire transcription programs. (
  • Establishing the role of histone modifications often involves analysing the abundance of the modification and the binding partners they interact with. (
  • ChIP-Seq has become a robust, routine and comprehensive technique for investigating and measuring various post-translational histone modifications across the entire genome. (
  • Nature Methods and Nature Biotechnology will host a live discussion on why histone modifications matter in health and disease. (
  • On February 26 we will discuss the importance of histone modifications from two aspects. (
  • Much chromatin research has centered on modifications to the core histones that regulate gene expression. (
  • In this review, we discuss how recent discoveries about chromatin modifications, particularly histone acetylation, are shaping our knowledge of cell biology and our understanding of the molecular circuitry governing tumor progression and consider whether recent insights may extend to novel therapeutic approaches. (
  • These posttranslational modifications of histones are often dynamic and reversible and are mediated by two antagonistic sets of enzymatic complexes that attach or remove the corresponding chemical groups in a site-specific manner. (
  • Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. (
  • Combinations of modifications are thought to constitute a code, the so-called histone code . (
  • [4] [5] Histone modifications act in diverse biological processes such as gene regulation , DNA repair and chromosome condensation ( mitosis ). (
  • Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. (
  • The combinatorial nature of histone amino-terminal modifications thus reveals a "histone code" that considerably extends the information potential of the genetic code. (
  • In particular, we center our discussion on examples where differences in "on-off" transcriptional states are reflected by differences in histone modifications that are either "euchromatic" (on) or "heterochromatic" (off) ( Fig. 1 A). We also point out that, despite many elegant genetic and biochemical insights into chromatin function and gene regulation in the budding yeast Saccharomyces cerevisiae , some of the heterochromatic mechanisms (e.g. (
  • Models for euchromatic or heterochromatic histone tail modifications. (
  • C ) Examples of combinatorial modifications in histone NH 2 -termini that are likely to represent "imprints" for active or inactive chromatin. (
  • The present understanding of epigenetic modifications through histone acetylation in PAH is very limited. (
  • We presented a mathematical model that consists of a standard positive feedback loop with changes of histone modifications during cell cycling. (
  • Some histone modifications have affected gene expressions that have been associated with cancer progression. (
  • Most of the global histone modification analyses done so far were performed on the two core histones H3 and H4 whereas the post-translational modifications of canonical H2A and H2B have been less well studied in metazoa. (
  • Histone protein modifications control fate determination during normal development and dedifferentiation during disease. (
  • Numerous studies have shown that distinct histone modifications in ESCs serve as hallmarks of pluripotency. (
  • However, so far it is still unknown whether the total histone content (as opposed to histone modifications) remains the same in cells of different developmental stage and differentiation capacity. (
  • We suggest that the difference in histone content is an additional hallmark of pluripotency, in addition to and besides histone modifications. (
  • Different histone modifications are known to mark chromatin in cells of different developmental stage. (
  • The peptides encompass 296 unique modifications on the four core histones (H2A, H2B, H3 and H4) and several histone variants. (
  • C ) Upper panel: graphic illustration of the position of CSL-binding peaks revealed by Chip-seq analysis for the KDM6B gene, utilizing ENCODE information for promoter and enhancer localization, as indicated by islands of histone H3 modifications (K4me3 and K27Ac) along with position of the transcription start site (TSS) ( 81 ) and coding exons (boxes). (
  • NH 2 -terminal tails of core histones extend outside of the core structure, exposing residues on these tails to dynamic posttranslational modifications (PTMs) that are critical. (
  • Histones may be chemically modified through the action of enzymes to regulate gene transcription. (
  • RJ: Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes. (
  • Typically, these reactions are catalyzed by enzymes with "histone acetyltransferase" (HAT) or " histone deacetylase " (HDAC) activity. (
  • To study the function of this residue independent from the enzymes that modify it, a 'histone replacement' system was used in Drosophila to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. (
  • Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, but also in their globular domains. (
  • These results highlight the use of the EpiTriton™ Histone Peptide Array for use in detecting the substrate specificity of histone modifying enzymes. (
  • Acetylation is a histone modification in which epsilon amino group of conserve lysine residue is modified with enzymes known as histone acetyltransferases (HATs). (
  • deacetylation-by HDAC (histone deacetylase): Acetylation tends to define the 'openness' of chromatin as acetylated histones cannot pack as well together as deacetylated histones. (
  • B. P. Ashburner, S. D. Westerheide, and A. S. Baldwin Jr., "The p65 (RelA) subunit of NF- κ B interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression," Molecular and Cellular Biology , vol. 21, no. 20, pp. 7065-7077, 2001. (
  • Cytoplasmic I κ B α Increases NF- κ B-independent transcription through binding to histone deacetylase (HDAC) 1 and HDAC3," Journal of Biological Chemistry , vol. 278, no. 47, pp. 46541-46548, 2003. (
  • Little is known about the contribution of histone deacetylase (HDAC) activity to the development of pulmonary arterial hypertension, a condition characterized by profound structural remodeling of pulmonary arteries and arterioles. (
  • Sulforaphane has a novel chemopreventive mechanism in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). (
  • In the search for new treatments, recent attentions have turned to drug repurposing opportunities, including study of the histone deacetylase (HDAC) inhibitor class of agents. (
  • Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflammatory gene expression by impairing transcription factor recruitment," Immunology , vol. 122, no. 4, pp. 596-606, 2007. (
  • The invention provides methods for assessing the efficacy of histone deacetylase inhibitors using biomarkers which can be used in human clinical trials and which are more quantitative, easy to be used and more relevant to clinical outcome for PD monitoring than existing assays. (
  • Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. (
  • This project studies the anti-cancer activities of a new class of drugs known as histone deacetylase inhibitors (HDACi) with the aim of using them in a more rational way for the treatment of cancer. (
  • The particular class of chemotherapeutic drugs that will be studied are called histone deacetylase inhibitors (HDACi) that have already shown promise in both laboratory experiments and in pre-clinical trials in patients. (
  • Ginsenoside 20(s)-Rh2 as potent natural histone deacetylase inhibitors suppressing the growth of human leukemia cells. (
  • Several classes of histone deacetylase inhibitors have been isolated and are currently undergoing evaluation as potential therapeutic modalities in the treatment of cancer. (
  • SMMC-7721 cells were treated with EPZ-6438 (1 μM) alone or in combination with histone acetyltransferase inhibitors C646 (5 μM) or SGC-CBP30 (5 μM) for 6 days. (
  • Along with a central globular domain, histone H2B has two[verification needed] flexible histone tails that extend outwards - one at the N-terminal end and one at C-terminal end. (
  • The main players in this story have been defined physically and genetically and include positioned nucleosomes, interactions of the histone tetramer (H3-H4)2 with DNA, the N-terminal tails of histones H3 and H4, and a large general activator complex. (
  • One of the most thoroughly studied modification of histone tails is the acetylation at lysine residues [ 5 ]. (
  • Of these, the best known modification is acetylation of the histone tails. (
  • The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution , all featuring a ' helix turn helix turn helix' motif (DNA-binding protein motif that recognize specific DNA sequence). (
  • Archaeal histone only contains a H3-H4 like dimeric structure made out of the same protein. (
  • Histones do not occur in vertebrate sperm cells (see protamine ) or in bacteria, although a very similar protein has been found in the genome of the archaebacterium Thermoplasma. (
  • Histone H2B is a lightweight structural protein made of 126 amino acids. (
  • Histone H2B is a structural protein that helps organize eukaryotic DNA. (
  • The strand of DNA winds around a histone octomer protein. (
  • Histone 1 exists as a histone linker protein and is associated at the DNA entrance and exit binding to the linker DNA. (
  • In their Perspective, Cirillo and Zaret discuss new findings that highlight a fifth type of histone, the linker histone H1, which is now shown to work with the Msx1 homeodomain protein to regulate the differentiation of muscle progenitor cells ( Lee et al . ). (
  • [1] A possible homolog of Dot1 was found in archaea which shows the ability to methylate archaeal histone-like protein in recent studies. (
  • Researchers in the Chromatin Structure and Function Lab at the Institute for Research in Biomedicine (IRB Barcelona) have identified the histone BigH1 as a key protein in stem cell differentiation to male sex cells. (
  • The histones do not have any tag and are not produced or purified as a fusion protein. (
  • They report that the tumor suppressor protein ING2 (inhibitor of growth 2) bound preferentially to histone 3 that was di- or trimethylated on lysine 4. (
  • The authors found that, in response to DNA damage, the ING2-containing histone deacetylase complex was recruited to the gene encoding cyclin D (a protein that promotes cell proliferation), and transcription of cyclin D was decreased. (
  • Hence, to maintain genome stability, histone synthesis is regulated at multiple levels-transcriptionally, posttranscriptionally and by modulating protein stability. (
  • Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. (
  • Furthermore, Hat2p is a WD40 repeat protein, which is found in many histone modifier complexes. (
  • Their findings, published last week in Science Express, follow a recent series of discoveries by several international genome sequencing consortiums that directly links a mutated histone protein to a rare brain stem cancer in children called DIPG. (
  • Mutation of a nonsirtuin histone deacetylase, Rpd3 , restored Sir-protein-based silencing in the absence of Sir2 's catalytic activity. (
  • The researchers examined the protein ZMYND8, which, as a histone "reader," can recognize these histone changes, potentially influence gene expression and head off metastasis. (
  • In humans, this protein has a Uniprot ID of P16104 and has an annotated function: 'Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. (
  • that histone content is reduced in the absence of the chromatin protein HMGB1. (
  • EpiCypher´s EpiTriton™ Histone Peptide Array platform is designed for rapid and high-throughput screening of effector protein, antibody and enzyme interactions with a comprehensive library of combinatorially-modified and biotinylated histone peptides immobilized on a streptavidin-coated glass slide. (
  • Every EpiTriton™ Histone Peptide Array contains more than 292 histone peptides spotted 18 times each for high quality detection and analysis of antibody or protein binding or enzyme activity. (
  • Histone H1-derived peptide phosphorylated by protein kinase A, is a substrate for CDK2 and CDK5 (cyclin dependent kinase 5) and PKA. (
  • [1] Histones associate with DNA to form nucleosomes , which themselves bundle to form chromatin fibers, which in turn make up the more familiar chromosome . (
  • histone H2B isoforms can be added to nucleosomes at other times during the cell cycle. (
  • Due to their intrinsic disorder, the CTDs are usually not resolved in X-ray crystallography and cryo-electron microscopy (cryo-EM) data for nucleosomes containing linker histones. (
  • How Are Histones Related to Nucleosomes? (
  • Histone 1 serves to help bind nucleosomes in order to further compact the chromatin. (
  • The complexes are further compacted by a factor of four by a linker histone that binds the DNA between the nucleosomes, organizing them into a coil. (
  • The removal of histones, including histone dimers, from nucleosomes within chromatin. (
  • The catalytic activity of Sir2 is necessary for the deacetylation of histone H4 N-terminal lysine residue 16 (H4K16) in nucleosomes at silenced loci. (
  • Acetylated histones and nucleosomes represent a type of epigenetic tag within chromatin . (
  • For a long time the amount of histones in a nucleus has been tacitly considered a fixed parameter, essentially corresponding to the length of DNA to be packaged into nucleosomes. (
  • The interaction between histones and DNA is fundamental for the packaging of DNA around nucleosomes to form chromatin. (
  • Similarly, the combination of phosphorylation of serine residue 10 and acetylation of a lysine residue 14 on histone H3 is a tell-tale sign of active transcription . (
  • A cyclin E-CDK2 substrate called NPAT has been found to be associated with histone gene clusters, and cyclin E-CDK2 bolsters activation of histone gene transcription by NPAT. (
  • Acetylation of histones is correlated to areas where transcription is occurring. (
  • This review discusses our current understanding of histone acetyltransferases (HATs) or acetyltransferases (ATs): their discovery, substrate specificity, catalytic mechanism, regulation, and functional links to transcription, as well as to other chromatin-modifying activities. (
  • Ubiquitinated histone H2B is often found in regions of active transcription. (
  • Specifically, the ubiquitin on histone H2B opens up and unfolds regions of chromatin allowing transcription machinery access to the promoter and coding regions of DNA. (
  • Histones are also involved in controlling which sequences of DNA are turned on for transcription of RNA. (
  • 1-3 Histone hyperacetylation is correlated with increased transcription, whereas hypoacetylation correlates with transcriptional repression. (
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to map histone marks and transcription factor binding throughout the genome. (
  • Figure 1: Rapid and robust analysis of histone marks and transcription factors by ChIPmentation. (
  • Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. (
  • In the present study, we show that direct and functional interaction of histone chaperone and DNA-binding transcription factor leads to promoter region-specific histone incorporation and inhibition of histone acetylation. (
  • We report here that the DNA-binding transcription factor Krüppel-like factor 5 (KLF5) interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene. (
  • Collectively, we have identified a novel histone chaperone, ANP32B, and through analysis of the actions of this factor show a new mechanism of promoter region-specific transcriptional regulation at the chromatin level as mediated by the functional interaction between histone chaperone and DNA-binding transcription factor. (
  • The deacetylase modifies nearby histones and may thereby repress transcription. (
  • With this outburst of knowledge, histone chaperones are now placed at the center of gene regulation, having roles to play in DNA replication, repair and transcription. (
  • Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation. (
  • 7 Histone acetyltransferases catalyze the acetylation of lysine residues, neutralizing positive charges, relaxing chromatin structure, and increasing accessibility to transcription machinery. (
  • Mechanistically, Fzr interacts with chromatin-associated histone H2B to enhance H2B ubiquitination in the Myc promoter and promotes Myc transcription. (
  • Modulation of chromatin structure via histone modification plays an important role in the regulation of transcription in eukaryotes. (
  • Cells with reduced histones, as expected, have a more accessible chromatin and increased transcription. (
  • It is worth noting that regulating gene transcription through the modification of both chromatin structure and histones is the main function. (
  • We have identified molecular mechanisms by which mutant huntingtin alters histone monoubiquitylation and show that uH2A and uH2B have opposite effects on transcription in mouse and cell culture models of HD. (
  • Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B. (
  • Histone acetyltransferases. (
  • Histone modification provides an epigenetic mechanism that enables a range of essential healthy and disease-related processes to be regulated. (
  • This research uncovers an epigenetic mechanism, involving one slightly-modified, "variant" histone, that makes learning possible by facilitating the genetic changes necessary for neurons to form connections," says study author C. David Allis, Joy and Jack Fishman Professor and head of the Laboratory of Chromatin Biology and Epigenetics. (
  • Based in Palo Alto, Calif., PrognosDx's epigenetic technology is based on the predictive power of global histone modification patterns and is licensed from the University of California, Los Angeles . (
  • Long-term changes in histone/DNA interaction cause epigenetic effects. (
  • We now have a model for the promotion of brain stem cancers through aberrant epigenetic silencing through the inhibition of PRC2 by a mutant histone," says Allis. (
  • Additionally, histone variants can also be posttranscriptionally modified similar to canonical histones =-=(56)-=- and have been proposed to play a role in establishing and maintaining epigenetic memory (49, 56, 109). (
  • Background- Epigenetic programming, dynamically regulated by histone acetylation, is a key mechanism regulating cell proliferation and survival. (
  • Aberrant epigenetic changes such as the histone acetylation state influence gene expression and play a role in regulating cell proliferation, migration, and survival and inflammation in several diseases, including cancer. (
  • HATs are responsible for acetylation of N-terminal histone tail whereas HDACs possess an opposite mode of action and act by removing the attached acetyl group. (
  • HDACs deacetylate histones. (
  • This requires that the HATs and HDACs must act continuously on the affected histone tail. (
  • Two H2A/H2B heterodimers interact with an H3/H4 tetramer to form the histone octamer (1,2). (
  • For example, phosphorylation of serine residues 10 and 28 on histone H3 is a marker for chromosomal condensation. (
  • The attachment of methyl groups occurs predominantly at specific lysine or arginine residues on histones H3 and H4. (
  • In histone acetylation and deacetylation , the histones are acetylated and deacetylated on lysine residues in the N-terminal tail as part of gene regulation . (
  • Drs. Mullen & Marzluff demonstrate that uridine residues are added to the 3' end of histone mRNAs, after which the transcript is decapped and degraded at both ends by components of the general mRNA decay machinery. (
  • Acetylation of lysine residues within these N-terminal domains by histone acetyl-transferases (HATs), is associated with transcriptional activation. (
  • Histones are subdivided into canonical replication-dependent histones that are expressed during the S-phase of cell cycle and replication-independent histone variants , expressed during the whole cell cycle. (
  • Complex multicellular organisms typically have a higher number of histone variants providing a variety of different functions. (
  • Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development. (
  • Histone variants from different organisms, their classification and variant specific features can be found in "HistoneDB 2.0 - Variants" database. (
  • While only a few isoforms of histone H2B have been studied in depth, researchers have found that histone H2B variants serve important roles. (
  • There are sixteen variants of histone H2B found in humans, thirteen of which are expressed in regular body cells and three of which are only expressed in the testes. (
  • All variants of histone H2B contain the same number of amino acids, and the variations in sequence are few in number. (
  • Histone variants of H2B can be explored using "HistoneDB with Variants" database. (
  • Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis. (
  • In contrast, variants of histone H1 differ between males and females in mice and in humans. (
  • The histone BigH1, which we have studied in Drosophila melanogaster, shows most resemblance to the germ line variant of human females but it also shows some similarities to variants of the male germ line," explains Albert Carbonell, postdoctoral fellow and first author of the paper. (
  • Five major types of histone, including one called H3, are known, and researchers have become interested in the function of variants of these histones, which are often very similar to their standard counterparts. (
  • Kamakaka RT, Biggins S. Histone variants: deviants? (
  • There are five families of histones which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). (
  • Location and function of linker histones. (
  • The linker histones, H1 and its variant forms, have been implicated in the formation of higher orders of chromatin structure and gene repression. (
  • AnaSpec, the world s largest provider of on-demand GO peptides is pleased to announce the rapid expansion of our histone peptide selection. (
  • KLH-conjugated linear peptide corresponding to the N-terminus of human Histone H4 trimethylated at Lys20. (
  • Immunohistochemical analysis of paraffin-embedded human lymphoma using Tri-Methyl-Histone H3 (Lys27) (C36B11) Rabbit mAb in the presence of non-methyl peptide (left) or K27 tri-methyl peptide (right). (
  • Extensive validation and purification of peptides is performed prior to histone peptide array printing to ensure the highest quality product for your studies. (
  • Each EpiCypher EpiTriton™ Histone Peptide Array contains 296 biotinylated histone peptides (20 amino acids in length or more) immobilized on a streptavidin-coated glass slide. (
  • A recombinant histone lysine 9 methyltransferase was used to methylate peptides on the EpiTriton™Histone Peptide Array. (
  • This is a FAM-labeled Histone H1-derived peptide (Ab/Em = 494/521 nm). (
  • Front view of the human enzyme Histone Lysine N-Methyltransferase, H3 lysine-4 specific. (
  • Active site of Histone Lysine N-Methyltransferase. (
  • Instead of SET, non-SET domain-containing histone methyltransferase utilizes the enzyme Dot1. (
  • Maternal contribution of the histone methyltransferase Enhancer of zeste , the enzymatic component of Polycomb repressive complex 2 , is required for active propagation of H3K27me3 during early embryogenesis. (
  • BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases. (
  • A role for histone deacetylase activity in HDAC1-mediated transcriptional repression," Proceedings of the National Academy of Sciences of the United States of America , vol. 95, no. 7, pp. 3519-3524, 1998. (
  • The main mammalian histone subtypes ( H2A, H2B, H3, and H4 ) and the linker H1 are located in different gene clusters. (
  • also found the PHD domain to be important for recognition of methylated histone H3 in mammalian cells. (
  • In the January 1st issue of G&D, Drs. Thomas Mullen and William Marzluff (UNC Chapel Hill) lend new insight into the degradation of mammalian histone mRNA. (
  • Histone Acetyltransferase Inhibitor II shows anti-acetylase activity in mammalian cells. (
  • This is the first report to demonstrate hPRC1L as a huntingtin-interacting histone modifying complex and a crucial role for histone monoubiquitylation in mammalian brain gene expression, which broadens our understanding of histone code. (
  • However, the role for histone monoubiquitylation in the regulation of mammalian gene expression is primarily unknown. (
  • This is the first report to show that histone monoubiquitylation regulates mammalian brain gene expression. (
  • Recent biochemical and genetic studies have identified several large, multisubunit enzyme complexes responsible for bringing about the targeted acetylation of histones and other factors. (
  • How the histones are packaged up into higher order complexes is largely unknown. (
  • At high magnification these DNA-histone complexes look like a series of beads on a string. (
  • Specific regulatory molecules other than the basal transcriptional machinery exist that can associate with nucleosomal DNA and initiate a chain of events that disrupt repressive histone-DNA complexes. (
  • I. Rahman, J. Marwick, and P. Kirkham, "Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF- κ B and pro-inflammatory gene expression," Biochemical Pharmacology , vol. 68, no. 6, pp. 1255-1267, 2004. (
  • This histone deacetylation model makes the simple prediction that preemptively removing Sir2 's H3 and H4 acetyl substrates, by mutating these lysines to unacetylatable arginines, or removing the acetyl transferase responsible for their acetylation, should restore silencing in the Sir2 catalytic mutant. (
  • The source of the acetyl group in histone acetylation is Acetyl-Coenzyme A , and in histone deacetylation the acetyl group is transferred to Coenzyme A. (
  • It uses material from the Wikipedia article "Histone_acetylation_and_deacetylation" . (
  • GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. (
  • C646 is an inhibitor for histone acetyltransferase , and inhibits p300 with a K i of 400 nM in a cell-free assay. (
  • Histone Acetyltransferase Inhibitor II (HAT Inhibitor II, compound 2c) is a potent, selective and cell-permeable p300 histone acetyltransferase (HAT) inhibitor with IC50 of 5 μM. (
  • CPTH2 is a potent histone acetyltransferase (HAT) inhibitor modulating Gcn5p network. (
  • WM-8014 is a highly potent inhibitor of histone acetyltransferase KAT6A with an IC50 of 8 nM. (
  • Anacardic Acid (6-pentadecylsalicylic Acid) is a potent inhibitor of p300 and p300/CBP-associated factor histone acetyltranferases , which also has antibacterial activity, antimicrobial activity, prostaglandin synthase inhibition, and tyrosinase and lipoxygenase inhibition. (
  • P300/CBP-IN-3 is an inhibitor of p300/CBP histone acetyltransferase. (
  • Ginkgolic acid, toxic phenolic compounds present in the fruits and leaves of Ginkgo biloba L., is a potent sumoylation inhibitor also reported to inhibit histone acetylation transferase (HAT) . (
  • For analysis of histone antibody specificity, you need a primary antibody to a histone modification and a labeled (fluorescent or HRP-conjugated) secondary antibody recognizing the primary antibody. (
  • This review will focus on the current knowledge we have about the role of histone chaperones in regulating cellular processes and their relation to disease. (
  • Specific regulation of histone incorporation/eviction by histone chaperones on the promoter (e.g., region specific) is still poorly understood. (
  • The regulation of histone synthesis in the cell cycle. (
  • Regulation of histone gene expression in budding yeast. (
  • Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3. (
  • Histone antibodies are autoantibodies . (
  • These are antibodies produced by a person's own immune system that target his or her own histones. (
  • This test detects the presence of histone antibodies in the blood. (
  • Histone autoantibodies are one of several types of antinuclear antibodies (ANA) . (
  • Drugs can stimulate the production of histone antibodies in some people and can cause a type of lupus called drug-induced lupus erythematosus. (
  • Up to 95% of those with drug-induced lupus will have histone antibodies. (
  • Classically histone antibodies give a homogeneous pattern on indirect IF. (
  • Histone antibodies are of limited value in distinguishing between SLE and drug-induced lupus. (
  • Histones form part of the chromosomal material of eukaryotic cells and appear to play an important, but as yet incompletely understood, role in gene regulation. (
  • In addition, histones play important roles in gene regulation and DNA replication. (
  • Histones act as spools around which DNA winds, and play a role in gene regulation . (
  • Normal stoichiometry of histone dimer sets is necessary for high fidelity of mitotic chromosome transmission. (
  • d ensure that each daughter chromosome would likely inherit a substantial proportion of the modified histones, which could then promote similar modification of new histones in the immediate vicinity (=-=Henikoff et al. (
  • Phosphorylation of histone H3 on Ser 10 is highly correlated with chromosome condensation during both mitosis and meiosis. (
  • Histone antibody testing is primarily used to support a diagnosis of drug-induced lupus , particularly in a person who is taking one of the medications mentioned above in the "What is being tested? (
  • Histone H3 Phosphorylation Antibody Panel Pack (H3Ser10, H3Ser28, H3Thr11) incl. (
  • Anti-Histone Deacetylase 1 (HDAC1) antibody can be used in chromatin immunoprecipitation. (
  • Anti-Histone Deacetylase 1 (HDAC1) antibody specifically recognizes histone deacetylase 1and reacts specifically with HDAC1 of human, rat and mouse. (
  • Histones are found in the nuclei of eukaryotic cells , and in certain Archaea , namely Euryarchaea , but not in bacteria . (
  • In Tetrahymena and Drosophila newly synthesized histone H3 is also deposited in several modified forms. (
  • Thus, we will need to pursue other model systems, such as Schizosaccharomyces pombe , Caenorhabditis elegans , Drosophila , and mice, to "crack" the histone code. (
  • This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair. (
  • This study found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. (
  • Experiments on Drosophila have shown that the histones that are normally bound to lipid droplets inside cells can be released to provide protection against infection. (
  • Catalysis of the reaction: acetyl-CoA + histone = CoA + acetyl-histone. (
  • We further show that recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. (
  • This tight regulation facilitates the creation of a very transient histone pool for replication-coupled chromatin assembly and ensures that histone synthesis is downregulated when DNA replication is completed or stalled due to replication inhibition. (
  • In order for the reaction to proceed, S-Adenosyl methionine (SAM) and the lysine residue of the substrate histone tail must first be bound and properly oriented in the catalytic pocket of the SET domain. (
  • Unlike the SET domain, which targets the lysine tail region of the histone, Dot1 methylates a lysine residue in the globular core of the histone, and is the only enzyme known to do so. (
  • PKA, Rsk-2 and Msk-1 are necessary for the histone H3 phosphorylation. (
  • Activation of both ERK and p38 MAP Kinase pathways by mitogenic stimuli, have been suggested to modulate the phosphorylation of histone H3. (
  • Acetylation at lysine 9 appears to have a dominant role in histone deposition and chromatin assembly in some organisms. (
  • Recent investigations suggest that gene expression modulated by histone acetylation might be associated with neurodegenerative processes [ 6 , 7 ]. (
  • Contains 1 H15 (linker histone H1/H5 globular) domain. (
  • The KDM5 family of transcriptional regulators are histone H3 lysine 4 demethylases that can function through both demethylase-dependent and -independent mechanisms. (
  • One family of transcriptional regulators that both recognizes and enzymatically modifies chromatin is the lysine demethylase 5 (KDM5) family of evolutionarily conserved histone demethylases. (
  • The class of lysine-specific histone methyltransferases is subdivided into SET domain-containing and non-SET domain-containing. (
  • A 3′ exonuclease that specifically interacts with the 3′ end of histone mRNA. (
  • FUS interacts directly with histone deacetylase 1 and plays a pivotal role in the DNA damage response. (
  • Histones also tend to be positively charged and this is largely due to the amine groups that are present on arginine and lysine amino acids. (
  • [1] Two major types of histone methyltranferases exist, lysine-specific (which can be SET ( S u(var)3-9, E nhancer of Zeste, T rithorax) domain containing or non-SET domain containing) and arginine-specific. (
  • Histone H3.3, an H3 variant that is found in all eukaryotes from yeast to human, is replication and cell cycle phase-independent and is the most common H3 in non-dividing cells. (
  • The genomic DNA of eukaryotes associates with histones to form chromatin . (
  • PKMTs methylate histone lysines. (
  • RMTs methylate histone arginines. (
  • [11] Due to structural constraints, Dot1 is only able to methylate histone H3. (
  • Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to 1 in human DNA). (
  • For example, each human cell has about 1.8 meters of DNA, (~6 ft) but wound on the histones it has about 90 micrometers (0.09 mm) of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes. (
  • Without histones, unwound DNA in chromosomes would be very long. (
  • These histones are crucial for efficient packaging of DNA, as well as the replication and segregation of chromosomes themselves. (
  • Histone mRNA is rapidly degraded at the end of S phase, but the mechanism by which this occurs has remained elusive, as metazoan histone mRNAs have a unique, conserved 3' stem-loop structure rather than the canonical 3' poly(A) tail. (
  • Our model reveals a simple mechanism of spontaneous cell-type switches through a stochastic histone modification inheritance during cell cycle. (
  • The structure of the Histone Deacetylase provides evidence of a common mechanism that is shared between the metal-dependent hydrolysis for active substrates. (
  • Here we show that alteration of histone monoubiquitylation is a key mechanism. (
  • We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. (
  • Histone H2B monoubiquitination: roles to play in human malignancy. (
  • Singh R, Mortazavi A, Telu KH, Nagarajan P, Lucas DM, Thomas-Ahner JM, Clinton SK, Byrd JC, Freitas MA, Parthun MR. Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis. (
  • wound on the histones, the diploid cell has about 90 micrometers (0.09 mm) of chromatin. (