Histone H3 Lysine 9 Methylation and HP1γ Are Associated with Transcription Elongation through Mammalian Chromatin

Vakoc, Christopher R.; Mandat, Sean A.; Olenchock, Benjamin A.; Blobel, Gerd A.

doi:10.1016/j.molcel.2005.06.011

Cited by 651 publications

(616 citation statements)

References 49 publications

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“…In addition to its physical association with RNA polymerase II, Vakoc et al (2005) confirmed the presence of H3K9Me3 within heterochromatic major satellite repeats. H3K9Me3 modifications may be unique among histone methylation modifications in being associated with both heterochromatin and actively transcribed genes (Eissenberg and Shilatifard, 2006).…”

Section: Discussionmentioning

confidence: 68%

“…This observation seems at variance with the well described association of H3K9Me3 with both constitutive (Peters et al, 2003) and facultative heterochromatin (Heard et al, 2001). Vakoc et al (2005) further reported that heterochromatin protein 1g (HP1g), which contains a chromo-domain predicted to recognize H3K9 methylation, is also present in the transcribed region and may form a complex with RNA polymerase II. Importantly, they demonstrated the specificity of the antibodies they used in their chIP experiments and ruled out cross-reactivity of H3K9Me3 with other markings that could have produced spurious results.…”

Section: Introductionmentioning

confidence: 80%

“…Our single gene ChIP confirmed the tiling array data in revealing robust H3K9Me3 signals among highly expressed genes such as HOXA9, MEIS1 and OTX2 in cells overexpressing these genes. In their first study Vakoc et al (2005) reported the strongest H3K9Me3 signals to be 0.5-1.5 kb downstream of the TSS of several genes. A more recent study emphasized the 3 0 location of H3K9Me3 markings in the polyA binding protein gene (Vakoc et al, 2006) and that regions of hyperacetylated histone H3 were relatively devoid of H3K9Me3.…”

Section: Discussionmentioning

confidence: 99%

“…The latter study termed these seemingly conflicting histone patterns 'bivalent' chromatin structures (Bernstein et al, 2006). Recently, Vakoc et al (2005) presented a surprising finding that H3K9Me3 was present in the transcribed region of eight genes that they examined. This observation seems at variance with the well described association of H3K9Me3 with both constitutive (Peters et al, 2003) and facultative heterochromatin (Heard et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The array interrogates 5 kb upstream and 1 kb downstream of the TSS of 683 genes including all known homeodomain transcription factors and many other cancer association genes (for example MAGE genes). The 5 0 -location of probes allows us to examine whether H3K9Me3 is restricted to the regions around and downstream of TSSs as predicted (Vakoc et al, 2005(Vakoc et al, , 2006. Gene expression was assessed by the Affymetrix HGU133 Plus 2.0 expression microarray.…”

Section: Introductionmentioning

confidence: 99%

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Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Zheng

Morrison

et al. 2007

Oncogene

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Histone H3 lysine 9 trimethylation (H3K9Me3) has been associated with transcriptional repression, but recent findings implicate this chromatin modification in transcriptional activation and mRNA elongation by RNA polymerase II. Here, we applied immunoprecipitation (IP) with a custom DNA tiling microarray containing many transcription factors important in development and cancer (for example homeotic genes; N ¼ 683 total genes) to explore the relationship between H3K9Me3 and other histone modifications with the differential expression of genes. Cancer cell lines derived from different tissues (2 leukemia, 2 medulloblastoma) were characterized with IP antibodies to H3K9Me3, H3K4 dimethylation (H3K4Me2) and H3K9 acetylation (H3K9Ac). MV4-11 is known to overexpress the HOXA9 and MEIS1 genes, whereas D283 overexpresses the OTX2 homeobox gene. Gene expression was assessed by Affymetrix U133 array. Mapping the number and size of histone markings demonstrated significant colocalization of H3K9Ac and H3K4Me2 with H3K9Me3, indicating a pattern of putative 'activating' and 'repressive' markings. The median site size was 600-821 bp and 72-95% or 53-80% of chromatin signal sites were located within 1 kb or 500 bp of transcription start sites (TSS), respectively. A relatively small number of genes displayed additional H3K9Me3 sites in the 5 0 -region distant from the TSS. Comparing genes with modification sites to those without sites in their promoters confirmed the positive associations of H3K9Ac and H3K4Me2 with gene expression and revealed that H3K9Me3 is associated with active genes rather than being a repressive marking as previously thought. The positive regulatory effect of all three types of modifications were quantitatively correlated with site size, and applied to absolute gene expression within a single cell line as well as relative expression among pairs of cell lines. Extended patterns of H3K9Me3 upstream of some genes (for example HOXA9 and OTX2) may result from the action of multiple promoter elements. We found an inverse relationship between promoter DNA hypermethylation and H3K9Me3 in three studied genes (HOXA9, TMS1, RASSF1A). The localization of H3K9Me3 downstream of the TSSs of expressed genes and not within promoter regions of hypermethylated and silenced genes is consistent with the proposed coupling of H3K9Me3 with RNA polymerase II. Our results indicate a need for revising aspects of the histone code involving H3 lysine methylation. Awareness of H3K9Me3 as a mark of gene activity, not repression, is especially important for the classification of human cancer using chromatin and histone profiles.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Zheng

Morrison

et al. 2007

Oncogene

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Epigenetics of the frozen brain: roles for lysine methylation in hypometabolism

Bloskie

Storey

2022

FEBS Letters

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Wood frog (Rana sylvatica) freeze tolerance necessitates metabolic rate depression, where costly processes such as gene transcription are commonly suppressed. Epigenetic mechanisms, such as histone lysine methylation, have recently been implicated in hypometabolic states of various animals, although they are underreported in nervous tissues. In the present study, we track the expression of eight lysine methyltransferases, as well as the activity on, and abundance of putative histone products across the freeze-thaw cycle and freeze-associated substresses (anoxia, dehydration) of wood frog brains. Our results suggest that hypomethylation of transcriptionally repressive H3K9 may be a key facet of metabolic recovery during the thawing of nervous tissue, which we speculate may have a positive effect on global gene transcription. Some nonhistone roles for lysine methylation are also proposed.

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