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70
A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125
, 2006
"... The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by ex ..."
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Cited by 269 (2 self)
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The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed ‘‘bivalent domains,’ ’ consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs
- Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang
"... Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kil ..."
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Cited by 194 (3 self)
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Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.
Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3
- Embo J
, 2004
"... Both DNA methylation and post-translational histone mod-ifications 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 ..."
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Cited by 64 (3 self)
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Both DNA methylation and post-translational histone mod-ifications 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 methyltransfer-ase, cause a reduction of CNG DNA methylation, suggest-ing 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 immunohistolocaliza-tion experiments, we found that H3K27 methylation colo-calizes with H3K9 methylation at CMT3-controlled loci.
A profile of histone lysine methylation across transcribed mammalian chromatin
- Mol. Cell Biol
, 2006
"... This article cites 79 articles, 31 of which can be accessed free ..."
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Cited by 26 (1 self)
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This article cites 79 articles, 31 of which can be accessed free
Histone code modifications on pluripotential nuclei of reprogrammed somatic cells
- Mol. Cell. Biol
, 2004
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Mapping Global Histone Methylation Patterns in the Coding Regions
, 2005
"... Histone methylation patterns in the human genome, especially in euchromatin regions, have not been systematically characterized. In this study, we examined the profile of histone H3 methylation (Me) patterns at different lysines (Ks) in the coding regions of human genes by genome-wide location analy ..."
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Cited by 20 (1 self)
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Histone methylation patterns in the human genome, especially in euchromatin regions, have not been systematically characterized. In this study, we examined the profile of histone H3 methylation (Me) patterns at different lysines (Ks) in the coding regions of human genes by genome-wide location analyses by using chromatin immunoprecipitation linked to cDNA arrays. Specifically, we compared H3-KMe marks known to be associated with active gene expression, namely, H3-K4Me, H3-K36Me, and H3-K79Me, as well as those associated with gene repression, namely, H3-K9Me, H3-K27Me, and H4-K20Me. We further compared these to histone lysine acetylation (H3-K9/14Ac). Our results demonstrated that: first, close correlations are present between active histone marks except between H3-K36Me2 and H3-K4Me2. Notably, histone H3-K79Me2 is closely associated with H3-K4Me2 and H3-K36Me2 in the coding regions. Second, close correlations are present between histone marks associated with gene silencing such as H3-K9Me3, H3-K27Me2, and H4-K20Me2. Third, a poor correlation is observed between euchromatin marks (H3-K9/K14Ac, H3-K4Me2, H3-K36Me2, and H3-K79Me2) and heterochromatin marks (H3-K9Me2, H3-K9Me3, H3-K27Me2, and H4-K20Me2). Fourth, H3-K9Me2 is neither associated with active nor repressive histone methylations. Finally, histone H3-K4Me2, H3-K4Me3, H3-K36Me2, and H3-K79Me2 are associated with hyperacetylation and active genes, whereas H3-K9Me2, H3-K9Me3, H3-K27Me2, and H4-K20Me2 are associated with hypoacetylation.
Chromatin of the Barr body: histone and non-histone proteins associated with or excluded from the inactive X chromosome
- Hum. Mol. Genet
, 2003
"... or excluded from the inactive X chromosome ..."
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Epigenetic inheritance and the intergenerational transfer of experience
- Psychol. Bull
, 2005
"... Currently, behavioral development is thought to result from the interplay among genetic inheritance, congen-ital characteristics, cultural contexts, and parental practices as they directly impact the individual. Evolutionary ecology points to another contributor, epigenetic inheritance, the transmis ..."
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Cited by 18 (0 self)
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Currently, behavioral development is thought to result from the interplay among genetic inheritance, congen-ital characteristics, cultural contexts, and parental practices as they directly impact the individual. Evolutionary ecology points to another contributor, epigenetic inheritance, the transmission to offspring of parental phenotypic responses to environmental challenges—even when the young do not experience the challenges themselves. Genetic inheritance is not altered, gene expression is. Organismic pathways for such transmission exist. Maternal stress during the latter half of a daughter’s gestation may affect not only the daughter’s but also grand-offspring’s physical growth. The author argues that temperamental variation may be influenced in the same way. Implications for theory and research design are presented along with testable predictions.
RJ: Histone modifying and chromatin remodelling enzymes in cancer and dysplastic syndromes. Hum Mol Genet 14
, 2005
"... Inactivation of tumour suppressor genes is central to the development of cancer. Although this inactivation was once considered to be secondary to intragenic mutations, it is now clear that silencing of these genes often occurs by epigenetic means. Hypermethylation of CpG islands associated with the ..."
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Cited by 13 (0 self)
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Inactivation of tumour suppressor genes is central to the development of cancer. Although this inactivation was once considered to be secondary to intragenic mutations, it is now clear that silencing of these genes often occurs by epigenetic means. Hypermethylation of CpG islands associated with the tumour suppressor genes was the first manifestation of this phenomenon to be described. It is apparent, however, that this is one of a host of chromatin modifications which characterize gene silencing. Although we know little about what determines which loci are affected, our understanding of the nature of the epigenetic marks and how they are established has blossomed. There is no compelling evidence that cancer ever develops by purely epigenetic means, but it is apparent that perturbations in the apparatus which establish the epigenome may contribute to the development of cancer. This review will focus on the role of two classes of chromatin remodelling enzymes, those that alter histones by the addition or removal of acetyl and methyl groups and those of the SWI/SNF family of proteins that change the topology of the nucleosome and its DNA strand via the hydrolysis of ATP, and we shall examine the consequence of mutations in, or mis-expression of, these factors. In some cases, mutations in these factors appear to play a direct role in cancer development. However, their general role as important intermediaries involved in regulating gene expression makes them attractive therapeutic targets. In exciting developments, it has been shown that inhibition of these factors leads to the reversal of tumour suppressor gene silencing and the inhibition of cancer cell growth.
USF1 recruits histone modification complexes and is critical for maintenance of a chromatin
- Downloaded from mcb.asm.org at UB Marburg on December 10, 2009 VAN DIJK ET
, 2007
"... These include: This article cites 46 articles, 29 of which can be accessed free at: ..."
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Cited by 12 (2 self)
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These include: This article cites 46 articles, 29 of which can be accessed free at:
