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H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells.

Karmodiya K, Krebs AR, Oulad-Abdelghani M, Kimura H, Tora L - BMC Genomics (2012)

Bottom Line: Our study also suggests that a subset of inactive promoters is selectively and specifically enriched for H3K14ac.This observation suggests that histone acetyl transferases (HATs) prime inactive genes by H3K14ac for stimuli dependent activation.In conclusion our study demonstrates a wider role for H3K9ac and H3K14ac in gene regulation than originally thought.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, BP 10142-67404 ILLKIRCH Cedex, CU de Strasbourg, France.

ABSTRACT

Background: 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.

Results: 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 H3K27ac, H3K9ac and H3K14ac can also differentiate active enhancers from inactive ones. Although, H3K9ac and H3K14ac, a hallmark of gene activation exhibit remarkable correlation over active and bivalent promoters as well as distal regulatory elements, a subset of inactive promoters is selectively enriched for H3K14ac.

Conclusions: Our study suggests that chromatin modifications, such as H3K9ac and H3K14ac, are part of the active promoter state, are present over bivalent promoters and active enhancers and that the extent of H3K9 and H3K14 acetylation could be driven by cis regulatory elements such as CpG content at promoters. Our study also suggests that a subset of inactive promoters is selectively and specifically enriched for H3K14ac. This observation suggests that histone acetyl transferases (HATs) prime inactive genes by H3K14ac for stimuli dependent activation. In conclusion our study demonstrates a wider role for H3K9ac and H3K14ac in gene regulation than originally thought.

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Correlation between the CpG content and the H3K9ac and H3K14ac level. 16026 CpG island sites associated with genes were sorted in descending order (top to bottom) on the basis of CpG content and the total H3, H3K9ac, H3K14ac and H3K4me3 were examined over them. CpG content on these sites correlates with the level of H3K9 and H3K14 acetylation as well as with the H3K4me3.
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Figure 3: Correlation between the CpG content and the H3K9ac and H3K14ac level. 16026 CpG island sites associated with genes were sorted in descending order (top to bottom) on the basis of CpG content and the total H3, H3K9ac, H3K14ac and H3K4me3 were examined over them. CpG content on these sites correlates with the level of H3K9 and H3K14 acetylation as well as with the H3K4me3.

Mentions: Cytosine-phosphate diester-guanine (CpG) islands are usually found at the 5’ end of the regulatory regions of genes [27]. CpG islands are GC rich, predominantly non-methylated and their content correlates with H3K4me3 chromatin modification. To explore the relationship between the CpG content and the levels of H3K9ac and H3K14ac, we took all the CpG island sites (16026) from UCSC genome browser [28] and sorted them according to their CpG content. On these CpG islands, which are sorted on the basis of their increasing CpG content, we looked for the H3K9ac and H3K14ac profile. We found that indeed CpG content correlates with the level of H3K9 and H3K14 acetylation, as acetylation over those sites increases in parallel with the CpG content (Figure3). This in turn suggests that the levels of H3K9 and H3K14 acetylations on the nucleosomes positioning around the TSSs of the promoters correlate with the CpG content of the underlying DNA sequence. This is in accordance with the fact that CpG enriched genes are generally housekeeping and are widely expressed [8,29].


H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells.

Karmodiya K, Krebs AR, Oulad-Abdelghani M, Kimura H, Tora L - BMC Genomics (2012)

Correlation between the CpG content and the H3K9ac and H3K14ac level. 16026 CpG island sites associated with genes were sorted in descending order (top to bottom) on the basis of CpG content and the total H3, H3K9ac, H3K14ac and H3K4me3 were examined over them. CpG content on these sites correlates with the level of H3K9 and H3K14 acetylation as well as with the H3K4me3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473242&req=5

Figure 3: Correlation between the CpG content and the H3K9ac and H3K14ac level. 16026 CpG island sites associated with genes were sorted in descending order (top to bottom) on the basis of CpG content and the total H3, H3K9ac, H3K14ac and H3K4me3 were examined over them. CpG content on these sites correlates with the level of H3K9 and H3K14 acetylation as well as with the H3K4me3.
Mentions: Cytosine-phosphate diester-guanine (CpG) islands are usually found at the 5’ end of the regulatory regions of genes [27]. CpG islands are GC rich, predominantly non-methylated and their content correlates with H3K4me3 chromatin modification. To explore the relationship between the CpG content and the levels of H3K9ac and H3K14ac, we took all the CpG island sites (16026) from UCSC genome browser [28] and sorted them according to their CpG content. On these CpG islands, which are sorted on the basis of their increasing CpG content, we looked for the H3K9ac and H3K14ac profile. We found that indeed CpG content correlates with the level of H3K9 and H3K14 acetylation, as acetylation over those sites increases in parallel with the CpG content (Figure3). This in turn suggests that the levels of H3K9 and H3K14 acetylations on the nucleosomes positioning around the TSSs of the promoters correlate with the CpG content of the underlying DNA sequence. This is in accordance with the fact that CpG enriched genes are generally housekeeping and are widely expressed [8,29].

Bottom Line: Our study also suggests that a subset of inactive promoters is selectively and specifically enriched for H3K14ac.This observation suggests that histone acetyl transferases (HATs) prime inactive genes by H3K14ac for stimuli dependent activation.In conclusion our study demonstrates a wider role for H3K9ac and H3K14ac in gene regulation than originally thought.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, BP 10142-67404 ILLKIRCH Cedex, CU de Strasbourg, France.

ABSTRACT

Background: 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.

Results: 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 H3K27ac, H3K9ac and H3K14ac can also differentiate active enhancers from inactive ones. Although, H3K9ac and H3K14ac, a hallmark of gene activation exhibit remarkable correlation over active and bivalent promoters as well as distal regulatory elements, a subset of inactive promoters is selectively enriched for H3K14ac.

Conclusions: Our study suggests that chromatin modifications, such as H3K9ac and H3K14ac, are part of the active promoter state, are present over bivalent promoters and active enhancers and that the extent of H3K9 and H3K14 acetylation could be driven by cis regulatory elements such as CpG content at promoters. Our study also suggests that a subset of inactive promoters is selectively and specifically enriched for H3K14ac. This observation suggests that histone acetyl transferases (HATs) prime inactive genes by H3K14ac for stimuli dependent activation. In conclusion our study demonstrates a wider role for H3K9ac and H3K14ac in gene regulation than originally thought.

Show MeSH