Histone H4-Lysine 20 Monomethylation Is Increased in Promoter and Coding Regions of Active Genes and Correlates with Hyperacetylation (original) (raw)
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Methylation of histone H3 Lys 4 in coding regions of active genes
Proceedings of The National Academy of Sciences, 2002
Posttranslational modifications of histone tails regulate chromatin structure and transcription. Here we present global analyses of histone acetylation and histone H3 Lys 4 methylation patterns in yeast. We observe a significant correlation between acetylation of histones H3 and H4 in promoter regions and transcriptional activity. In contrast, we find that dimethylation of histone H3 Lys 4 in coding regions correlates with transcriptional activity. The histone methyltransferase Set1 is required to maintain expression of these active, promoter-acetylated, and coding region-methylated genes. Global comparisons reveal that genomic regions deacetylated by the yeast enzymes Rpd3 and Hda1 overlap extensively with Lys 4 hypo-but not hypermethylated regions. In the context of recent studies showing that Lys 4 methylation precludes histone deacetylase recruitment, we conclude that Set1 facilitates transcription, in part, by protecting active coding regions from deacetylation.
Dynamic Regulation of Histone H3 Methylated at Lysine 79 within a Tissue-specific Chromatin Domain
Journal of Biological Chemistry, 2003
Post-translational modifications of individual lysine residues of core histones can exert unique functional consequences. For example, methylation of histone H3 at lysine 79 (H3-meK79) has been implicated recently in gene silencing in Saccharomyces cerevisiae. However, the distribution and function of H3-meK79 in mammalian chromatin are not known. We found that H3-meK79 has a variable distribution within the murine -globin locus in adult erythroid cells, being preferentially enriched at the active major gene. By contrast, acetylated H3 and H4 and H3 methylated at lysine 4 were enriched both at major and at the upstream locus control region. H3-meK79 was also enriched at the active cad gene, whereas the transcriptionally inactive loci necdin and MyoD1 contained very little H3-meK79. As the pattern of H3-meK79 at the -globin locus differed between adult and embryonic erythroid cells, establishment and/or maintenance of H3-meK79 was developmentally dynamic. Genetic complementation analysis in null cells lacking the erythroid and megakaryocyte-specific transcription factor p45/NF-E2 showed that p45/NF-E2 preferentially establishes H3-meK79 at the major promoter. These results support a model in which H3-meK79 is strongly enriched in mammalian chromatin at active genes but not uniformly throughout active chromatin domains. As H3-meK79 is highly regulated at the -globin locus, we propose that the murine ortholog of Disruptor of Telomeric Silencing-1-like (mDOT1L) methyltransferase, which synthesizes H3-meK79, regulates -globin transcription. Post-translational modification of core histones in chromatin represents a common epigenetic mechanism that controls diverse nuclear processes. An almost endless number of histone
Journal of Biological Chemistry, 2002
Histone N-terminal tails are post-translationally modified in many ways. At lysine residues, histones can be either acetylated or methylated. Both modifications lead to the binding of specific proteins; bromodomain proteins, such as GCN5, bind acetyl lysines and the chromodomain protein, HP1, binds methyl lysine 9 of histone H3. Here we show that the previously characterized transcriptional repressor complex NuRD (nucleosome remodeling and deacetylase) binds to the histone H3 N-terminal tail and that methylation at lysine 4, but not lysine 9, prevents binding. Given that lysine 4 methylation is found at sites of active transcription, these results suggest that a function of lysine 4 methylation is to disrupt the association of histones with a repressor complex.
Distribution and maintenance of histone h3 lysine 36 trimethylation in transcribed locus
PloS one, 2015
Post-translational modifications of core histones play an important role in the epigenetic regulation of chromatin dynamics and gene expression. In Saccharomyces cerevisiae methylation marks at K4, K36, and K79 of histone H3 are associated with gene transcription. Although Set2-mediated H3K36 methylation is enriched throughout the coding region of active genes and prevents aberrant transcriptional initiation within coding sequences, it is not known if transcription of one locus impacts the methylation pattern of neighbouring areas and for how long H3K36 methylation is maintained after transcription termination. Our results demonstrate that H3K36 methylation is restricted to the transcribed sequence only and the modification does not spread to adjacent loci downstream from transcription termination site. We also show that H3K36 trimethylation mark persists in the locus for at least 60 minutes after transcription inhibition, suggesting a short epigenetic memory for recently occurred t...
Histone lysine methylation: a signature for chromatin function
Trends in genetics : TIG, 2003
Abbreviations: ALL-1, acute lymphoblastic leukemia 1; ALR-1, ALL-1 related gene; Ash1, absent small or homeotic discs1; Dot1, disrupter of telomeric silencing; Dot1L, D. melanogaster, Drosophila melanogaster. ESET, SET domain bifurcated 1; Eu-HMTase, euchromatic histone methyltransferase 1; E(Z), enhancer of zeste; Ezh2, enhancer of zeste homolog 2; MLL, mixed lineage leukemia; NSD1, nuclear receptor binding SET domain protein 1; PR-set7, PR-SET domain containing protein 07; SETBD1, SET domain bifurcated 1; Set1, SET domain containing 1 Set2, SET domain containing 2; Set9, Suv39, suppressor of variegation 3 -9 homolog; Su(var)3-9, suppressor of variegation; S. cerevisiae, Saccharoymces cervisiae; S. pombe, Schizosaccharomycess pombe; Trx, trithorax. a Nomenclatures used are from original works describing histone lysine methyltransferase (HKMT) activity either in vivo or in vitro; enzymes discovered in plants, worms and frogs are not shown. b H3 and H4 refer to histones, the specific lysine residues are also indicated. c Ash1 exhibits H3-K4, H3-K9, and H4-K20 methylation activity. d Also called Set7 [72]. e Mouse homolog of human SETDB1.
Genome Research, 2011
The mammalian genome contains numerous regions known as facultative heterochromatin, which contribute to transcriptional silencing during development and cell differentiation. We have analyzed the pattern of histone modifications associated with facultative heterochromatin within the mouse imprinted Snurf-Snrpn cluster, which is homologous to the human Prader-Willi syndrome genomic region. We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously identified as a hallmark of actively transcribed regions, is deposited onto the silenced, maternally contributed 3-Mb imprinted region. We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification. In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts. This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin. Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.
Cell, 2002
and against the reversible nature of methylation and consider ways in which this modification may be dis-University of Cambridge Tennis Court Road placed from the histones if methylation were to be dynamically controlled. Cambridge CB2 1QR United Kingdom Methylation of Histones The major methylation sites within histone tails are the Methylation of histones mediates transcriptional sibasic amino acid side chains of lysine and arginine resilencing at heterochromatin sites and affects regulated dues (Kouzarides, 2002; Zhang and Reinberg, 2001). The transcription at euchromatic loci. So is the methyl positions of many of these methylated residues within group a permanent mark on histones, or can it be the histone N-terminal tails have now been mapped (Figremoved by an active process necessary for regulated ure 1A), and the histone methyltransferases (HMTs) pergene expression?