Histone h3k36 methylation. Nov 1, 2022 · 2.

Histone h3k36 methylation. Jan 31, 2020 · Histone marks control many cellular processes including DNA damage repair. Jan 8, 2025 · We find that H3K36 methylation reinforces expression of cell-type-associated genes to maintain specialized cell identity in intestinal epithelial cells. We investigated whether a causal relationship exists between splicing and chromatin modification by asking whether splice-site mutations affect the methylation of histone H3K36 … Currently, evidence has mounted that these histone marks also play important roles in the DDR. S8A). Oct 17, 2022 · High auxin stimulates callus formation through SET DOMAIN GROUP 8 (SDG8)-mediated histone H3K36 methylation Proposed working model of high auxin-SDG8 regulating callus formation. Trimethylation of H3K36 (H3K36me3) demarcates body regions of the actively transcribed genes, providing signals for modulating transcription fidelity, mRNA splicing and DNA damage repair; and di-methylation of H3K36 Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. May 25, 2018 · Here we report that unlike the K27M or K36M that affect global histone methylation, the giant cell tumors of the bone G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis), a mechanism distinct from known histone mutations. Thus, a clear understanding of the entire spectrum of histone methylations and their regulation is a prerequisite for understanding the epigenetic control of gene expression. Dec 15, 2008 · Here we show that Iws1 also recruits the HYPB/Setd2 histone methyltransferase to the RNAPII elongation complex and is required for H3K36 trimethylation (H3K36me3) across the transcribed region of the c-Myc, HIV-1, and PABPC1 genes in vivo. Its role in regulating cellular processes such as RNA splicing, DNA repair, and spurious transcription initiation underlies its broader tumor suppressor function. Dec 12, 2024 · During transcription, RNA polymerase II traverses through chromatin, and posttranslational modifications including histone methylations mark regions of active transcription. Sen et al. DNA damage-mediated methylation dynamics have been identified on several lysine residues including histone H3 Lysine 4 (H3K4), H3K9, H3K27, H3K36, H3K79 and histone H4 lysine 20 (H4K20me2) (Fig. It is a mark that indicates the tri- methylation at the 36th lysine residue of the histone H3 protein and often associated with gene bodies. Loss- and gain-of-function mutations in H3K36 methyltransferases are closely linked to human developmental disorders and various cancers. Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. Feb 14, 2025 · A histone methyltransferase, EARLY FLOWERING IN SHORT DAYS (EFS) is required for reproductive organs development via histone H3K36 methylation in the oil-seed type Brassica rapa (B. 2A and fig. In particular, the H3K36I mutation recapitulated H3K36M's impact on histone methylation and gene expression (Fig. Trimethylation of H3K36 (H3K36me3) demarcates body regions of the Oct 4, 2024 · The H3. In contrast, deletion of the K36me2/3 demethylase Rph1 increases Histone methylation is defined as a covalent modification that occurs at amino acid residues, specifically on the basic amino acids arginine and lysine of histones, regulated by histone methyl transferases. Covalent modifications of histones are essential to control a wide range of processes during development and adaptation to environmental changes. Feb 5, 2025 · Background SETD2 is the sole epigenetic factor responsible for catalyzing histone 3, lysine 36, tri-methylation (H3K36me3) in mammals. By mass spectrometric analyses of H3 purified from Tetrahymena thermophila and Saccharomyces cerevisiae (yeast), we find that H3K36 can be acetylated or Oct 29, 2021 · H3K36 methylation is a highly conserved histone mark and includes three methyl states, mono-, di-, and tri-methylation. May 4, 2018 · Here the authors show that reduction of H3K36 methylation in preadipocytes, both by H3. In yeast, Set2 catalyzes all three methylation states. , 2005). Aug 16, 2011 · A chromatin code appears to mark introns and exons with distinct patterns of nucleosome enrichment and histone methylation. DiFiore et al. To date, the intrinsic properties of NSD1 that determine its nucleosomal substrate selectivity and dimethyl H3K36 product specificity remain unknown. In this study, we show that depletion of histone H3K36 methylation by H3. These p … Feb 29, 2024 · Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. There are diverse clues showing H3K36me3 participates in DNA damage response by directly recruiting DNA repair machinery to set the chromatin at a Mar 20, 2025 · Retraction and replacement of 'Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers' The capacity of various H3K36 mutants to impair chondrocyte differentiation of MPCs was correlated to the magnitude of changes in H3K36 and H3K27 methylation (Fig. Better Jun 9, 2014 · Further, H3K36 modification is cell cycle regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs, while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. Oct 1, 2021 · Thus, recent structural studies suggest that unmodified H3K36 is required for unimpeded methylation of lysine-27 of histone H3 (H3K27) by the polycomb-repressive complex 2 (PRC2) (58, 59). These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, and Dec 23, 2020 · Cryo-electron microscopy structures of the nucleosome-bound NSD2 and NSD3 histone methyltransferases reveal the molecular basis of their histone modification activity, and show how mutations in The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. We produced high-resolution Mar 11, 2011 · The Sotos syndrome gene product, NSD1, is a SET domain histone methyltransferase that primarily dimethylates nucleosomal histone H3 lysine 36 (H3K36). Here, we use Jun 1, 2021 · Methylation of histones on different lysine residues is dynamically added by distinct writer enzymes, interpreted by reader proteins, and removed by eraser enzymes. In this point of view, we describe what is known about the distinct physiological roles of H3K36 methylation (H3K36me) states, which are regulated in vivo by Set2 and RNA polymerase 2 (Pol2). Loss- and gain-of-function mutations in May 30, 2024 · RETRACTED AND REPLACED: Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers Muhunden Jayakrishnan, Magdalena Havlová, Václav Veverka, May 13, 2016 · These cancer-associated H3 mutations (so-called “oncohistones”) map to, or close to, well-known sites of histone posttranslational modifications such as methylation of H3K27 and H3K36. Writers H3K36 writers are histone methyltransferases (HMTs) that contain a SET (Suppressor of variegation 3-9, Enhancer of Zeste, and Trithorax Jul 2, 2019 · Histone methylation regulates gene expression throughout animal development, governing processes as diverse as cell fate decisions, lineage specification, body patterning and organogenesis. Apr 3, 2012 · This Review provides a broad overview of the regulation of and by histone methylation. ABSTRACT Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. Apr 28, 2017 · This review summarizes enzymes responsible for histone lysine methylation and demethylation and how histone lysine methylation contributes to various biological processes. To further define the contribution of histone modi cations to pre-mRNA splicing in fi Saccharomyces , we probed a library of histone point mutants using a reporter to H3K36 methylation is a highly conserved histone mark and includes three methyl states, mono-, di-, and tri-methylation. These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, and DNA repair. address whether the distinct methyl-lysine states catalyzed by Set2 on nucleosomes have unique or shared functions in transcription and other cellular processes. Set2 —which was ini-tially identi fied as a nucleosomal histone methyltransferase from budding yeast whole cell extract24 —contains a SET domain, as well as an SRI domain that interacts with phosphorylated Ser2 and Ser5 of the Pol2 CTD. Aug 3, 2022 · Histone H3. At least eight kinds of HMTases have been identified to catalyze H3K36 methylation in higher eukaryotic cells. Mar 11, 2011 · Abstract The Sotos syndrome gene product, NSD1, is a SET domain histone methyltransferase that primarily dimethylates nucleosomal histone H3 lysine 36 (H3K36). Conversely, in higher eukaryotes, there are multiple H3K36 methyltransferases that are responsible for this mark. Histone lysine acetylation is a major mechanism by which cells regulate the structure and function of chromatin, and new sites of acetylation continue to be discovered. May 4, 2018 · The epigenetic mechanisms regulating adipose tissue development and function are poorly understood. 3K36M expression and depletion of H3K36 methyltransferase Nsd2, impairs adipogenesis by increasing H3K27me3. Mar 3, 2017 · Histone H3 lysine 36 methylation (H3K36me) is critical for epigenetic regulation and mutations at or near H3K36 are associated with distinct types of cancers. 2). It involves the mono (H3K36me1), di (H3K36me2), and/or tri-methylation (H3K36me3) of lysine 36 on histone H3 by methyltransferases. This process can activate or repress transcription, with specific methylation sites associated with different biological functions. H3K36 methylation is an evolutionary conserved process, however, in yeast, only one enzyme—HMT Set2 (SET domain containing protein-2 In Saccharomyces cerevisiae, the H3K4 and H3K36 methylation independently recruit histone acetyltransferase NuA3 to the actively transcribed genes, which also provide an accessible chromatin state for DNA repair 76. Histone H3K36me writer Histone H3K36me is highly conserved in eukaryotes 1 and is important for chromatin organization. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1L_BD), a plant homeod … Jan 9, 2024 · For example, although we examined alterations in H3K36me2 and H3K27me3, examining other histone modifications as well as DNA and RNA methylation changes on a genome-wide basis will add further nuance and granularity into how impaired H3K36 methylation impacts other key epigenetic modifications to drive these observed phenotypic changes. The mark is interpreted by epigenetic readers that assist transcription The methylation of histone H3 at lysine 36 (H3K36me) is essential for maintaining genomic stability. Becker, Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers, Nucleic Acids Research, Volume 52, Issue 13, 22 July 2024, Pages Jan 23, 2012 · Methylation of Lys36 on histone H3 (H3K36) is an important modification for multiple cellular processes. With the establishment of reference epigenomes, patterns of histone modifications were correlated with transcriptionally active or silenced genes. Here, Jha and Strahl identify methylation of histone H3 on lysine 36 mediated by the histone In this point of view, we describe what is known about the distinct physiological roles of H3K36 methylation (H3K36me) states, which are regulated in vivo by Set2 and RNA polymerase 2 (Pol2). H3K36 has functionally relevant acetylation and methylation states. Depiction of the transition between the different states or chromatin marks of lysine 36 of histone H3. 3K36M oncohistone mutation is a driver of chondroblastomas. Histone H3K36 writers and erasers Histone H3K36 is subject to mono-, di- and trimethylation, as well as demethylation and acetylation of lysine 36 of histone H3. In this review, we comprehensively evaluate histone methylation dynamics in male germ cells, from spermatogonia to sperm cells. To determine whether the effects on H3K36 and H3K27 methylation by G34 mutations are direct or indirect, we carried out in vitro methylation assays using recombinant histone proteins and purified SETD2 SET domain, p300 HAT domain and full-length EZH2 in reconstituted PRC2 complex. 7 Å structure of the catalytic domain of NSD1 presented here shows that a Homeostasis of H3K36 methylation. Here we identify and characterize histone H3K36 acetylation (H3K36ac). Here we elucidate a DSB repair function for transcription-coupled Set2 methylation at H3 lysine 36 (H3K36me). For example, histone methylation plays a key role in mediating plant responses to temperature, including alterations of flowering Mar 3, 2011 · Thus, a clear understanding of the entire spectrum of histone methylations and their regulation is a prerequisite for understanding the epigenetic control of gene expression. These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, Jun 30, 2016 · Together, these findings elucidate a role for H3K36 methylation in regulating H3K27 methylation and polycomb complex recruitment, and indicate that specific histone mutations are sufficient to promote sarcomagenesis by impairing MPC differentiation. The chromodomain protein MSL3 binds H3K36me3 to target X-chromosomal genes in male Drosophila for dosa … Jan 9, 2020 · Writers H3K36 writers are histone methyltransferases (HMTs) that contain a SET (Suppressor of variegation 3-9, Enhancer of Zeste, and Trithorax) domain and use S-adenosylmethionine to add methyl groups to histones (or other proteins) (Dillon et al. Histone methylation was first discovered in the context of transcription regulation in calf thymus cell extracts [5]. Jun 9, 2020 · Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethyla-tion (H3K36me1/2/3). To date, at least eight enzymes have been reported to methylate H3K36, and these can be Apr 12, 2022 · Fang et al. Jun 9, 2014 · Further, H3K36 modification is cell cycle regulated with Set2-dependent H3K36 methylation peaking in G1 when NHEJ occurs, while Gcn5-dependent H3K36 acetylation peaks in S/G2 when HR prevails. trilocularis) plant. SETD2 mutation promotes the epithelial-mesenchymal transition and is clinically associated with May 30, 2019 · Methylation of histone H3 lysine 36 (H3K36) plays crucial roles in the partitioning of chromatin to distinctive domains and the regulation of a wide range of biological processes. Nov 18, 2011 · Thus, the state of methylation at H3K36—me2 versus me3—may link modification of this residue to dramatically different functional consequences, and highlights the exquisite level of biological regulation that can be achieved by subtle changes in histone methylation. 3 G34R/V, IDH1 and/or SETD2 mutations, are central to the genesis of hemispheric HGGs in older children and young adults. H3K36M dominantly inhibits H3K36me on Jun 9, 2020 · Summary Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). Mar 31, 2025 · Histone methylation, on the other hand, can mark active genes by specific modifications, such as methylation of H3K4 and H3K36. Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). In Drosophila, the chromodomain protein MSL3 binds H3K36me3 at X-chromosomal genes to implement dosage compensati … Apr 12, 2021 · Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. find that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. 2, A to C and fig. During callus induction, the increased auxin accumulates SDG8 expression through a TIR1/AFBs-based transcriptional regulation. To further define the contribution of histone modifications to pre-mRNA splicing in … Mar 6, 2025 · The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Histone protein H3 lysine 36 trimethylation (H3K36me3), which is established by Nov 1, 2022 · 2. Jun 9, 2014 · Abstract Histone modifications are major determinants of DNA double-strand break (DSB) response and repair. Jul 1, 2023 · Potential defects in correctly establishing histone methylation marks in H3K4, H3K9, H3K27, H3K36, H4R3, and H4K20 residues in male germline cells during spermatogenesis may result in the development of infertility. After the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of its target genes known to block The most extensively studied histone methylation sites include histone H3 lysine 4 (H3K4), H3K9, H3K27, H3K36, H3K79 and H4K20. 3 with a K36M substitution (H3. Set2-dependent H3K36me Histone H3K36 is highly methylated along the tran-scriptional unit in chromatin. Mar 6, 2025 · The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Methylation of histone H3 lysine 36 (H3K36) plays crucial roles in the partitioning of chromatin to distinctive domains and the regulation of a wide range of biological processes. Apr 1, 2025 · This is a retraction and replacement of: Muhunden Jayakrishnan, Magdalena Havlová, Václav Veverka, Catherine Regnard, and Peter B. Mar 20, 2025 · Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. 3K36M in preadipocytes inhibits adipogenesis by increasing H3K27me3 to prevent the induction of C/EBPα and other targets of the … Jun 6, 2020 · Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). com. The mark is interpreted by epigenetic readers that assist transcription and safeguard the integrity of the chromatin fiber. Loss- and gain-of-function mutations in H3K36 methyltransferases are closely linked to hum … Jan 29, 2016 · Utilizing the reporter to probe for splicing defects in a library consisting of hundreds of synthetic histone point mutants, 45 we identified several histone point mutations displaying splicing-like defects. Sites of arginine methylation include H3R2, H3R8, H3R17, H3R26 and H4R3. By contrast, in higher … H3K36me3 H3K36me3 is an epigenetic modification to the DNA packaging protein Histone H3. cerevisiae, Set2 is the sole histone methyltransferase that acts on H3K36 [13]. provide evidence that expression of H3. 3K36M) was identified as an onco-histone that affects the global H3K36 methylation level through its inhibitory effect on histone H3K36 methyltransferases Abstract A chromatin code appears to mark introns and exons with distinct patterns of nucleosome enrichment and histone methylation. Here, we use Nov 5, 2024 · Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. . We measure combinatorial H3K27 and H3K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones. Sep 4, 2019 · Enzymes that catalyse CpG methylation in DNA, including the DNA methyltransferases 1 (DNMT1), 3A (DNMT3A) and 3B (DNMT3B), are indispensable for mammalian tissue development and homeostasis1–4 Apr 1, 2025 · Abstract. We investigated whether a causal relationship exists between splicing and chromatin modification by asking whether splice-site mutations affect the methylation of histone H3K36. S8, A to C). 3K36M leads to a loss of epigenetic memory in human cell models through inhibition of H3K36 methylases and concordant loss of CpG methylation. However, it was not known whether the different methylation states of H3K36 have distinct biological functions. This epigenetic mark has widespread, dynamic roles in plant development and environmental responses. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum Lubin Jiang1*, Jianbing Mu2*, Qingfeng Zhang3,4,5, Ting Ni6, Prakash Dec 9, 2019 · The structure also explains how human PWWP domain-containing proteins are recruited to H3K36-methylated regions of the genome for transcription, histone acetylation and methylation, and for DNA Methylation of H3K36 is a key histone mark and has been widely associated with active chromatin but also with transcriptional repression, alternative splicing, DNA replication and repair, DNA methylation and the transmission of memory of gene expression from parents to offspring during development (reviewed in [41]). However, it was not known whether the … May 13, 2016 · Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation. This review will focus primarily on the active histone mark H3K36me3 in the regulation of DNA damage repair and the maintenance of genomic stability after DNA damage. Known enzymes found in mammals able to add or removemethyl groups are highlighted. Indeed, this methylation mark is essential for proper transcription, recombination, and DNA damage response. The mark is interpreted by epigenetic readers that assist transcription and safeguard chromatin fiber integrity. There are diverse modifications at H3K36 and have many important biological processes. Their studies show that H3K36me1/2 and H3K36me3 act redundantly in many cellular contexts, including preventing antisense transcription during nutrient stress. This review will elaborate on current advances in understanding H3K36 methylation and related molecular players during various chromatin-templated cellular processes, their crosstalks with other chromatin factors, as well as their deregulations in the diseased contexts. Jul 22, 2024 · Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. Jan 28, 2020 · We take a quantitative computational modeling approach to describe propagation of histone H3K27 and H3K36 methylation states. 7 Å structure of the catalytic domain of NSD1 presented here shows that a regulatory Taken together, our results suggest that mutations disrupting the histone code at H3K36, including H3. This mark is interpreted by the cell in several crucial biological processes including gene transcription May 18, 2022 · The methylation of histone H3 at lysine 36 (H3K36me) is essential for maintaining genomic stability. These modifications recruit or repel chromatin effector proteins important for transcrip-tional fidelity, mRNA splicing, and DNA repair. H3K36 are very diverse and have roles in many important biological processes. Methylation of H3K36 is found in species ranging from yeasts to mammals. Jan 9, 2020 · Post-translational methylation of H3 lysine 36 (H3K36) is an important epigenetic marker that majorly contributes to the functionality of the chromatin. Sinha et al. The chromodomain protein MSL3 binds H3K36me3 to Jun 3, 2021 · Signal Transduction and Targeted Therapy - Targeting H3K36 methyltransferases NSDs: a promising strategy for tumor targeted therapy Oct 21, 2024 · Discussion As a histone methyltransferase, SETD2 can catalyze the trimethylation of histone H3 lysine 36 (H3K36) and participate in some biological processes, such as transcriptional elongation, alternative splicing, DNA repair and so on [10]. Cells devoid of Set2/H3K36me are hypersensitive to DNA-damaging agents and site-specific DSBs, fail to properly activate the DNA-damage checkpoint, and show genetic interactions Set2 and H3K36 methylation In S. Created with BioRender. These defects also mimic those seen in deletion mutants of specific histone modification- and chromatin remodeling-enzymes, including set2 Δ. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2 … Here, we find that high auxin induces callus through a H3K36 histone methylation-dependent mechanism, which requires the methyltransferase SET DOMAIN GROUP 8 (SDG8). The 1. Jan 1, 2025 · H3K36 methylation is a critical histone modification involved in transcription regulation. A balance between dynamism and stability is highlighted by links to disease and ageing, and current studies The methylation of histone H3 at lysine 36 (H3K36me) is essential for maintaining genomic stability. Methylation of histone H3 lysine 36 (H3K36) plays crucial roles in the partitioning of chromatin to distinctive domains and the regulation of a wide range of biological processes. Jun 9, 2014 · Chromatin modifications play a fundamental role in regulating the cellular response to DNA damage. rapa var. Oct 29, 2025 · Finally, continued transcription leads to upstream nucleosome reassembly, partial dissociation of the histone chaperone FACT and sequential methylation of both H3 tails, completing H3K36me3 Apr 1, 2025 · To study the genomic distribution of the histone H3K36 methylation states (and their corresponding HMTs), we generated high-resolution MNase chromatin immunoprecipitation (ChIP-seq) profiles in male Drosophila S2 cells. show an adaptive mechanism by which the nutrient-sensitive methylation of H3K36 plays a role in the metabolic balance of phospholipid synthesis and nucleotide metabolism in the redox environment. Here, we use engineered forms of Set2 that produce different lysine methylation states to identify unique and shared functions for H3K36 modifications. A strong correlation exists between the genome‐wide distribution of DNA and histone Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Jun 1, 2022 · In this review, we focus on the four major histone methylation modifications in Arabidopsis H3, H3K4, H3K9, H3K27, and H3K36, and summarize current knowledge of the dynamic regulation of these modifications, with an emphasis on the biochemical and structural perspectives of histone methyltransferases and demethylases. ad vwdit 0wch uphsz 2xwsvvl t0gvsm hjm yycf xexw gs77c