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Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin accessibility and histone H3 and H3.3 occupancy at active chromatin regions.

Siggens L, Cordeddu L, Rönnerblad M, Lennartsson A, Ekwall K - Epigenetics Chromatin (2015)

Bottom Line: CHD2 depletion causes increased histone H3 and reduced histone variant H3.3 occupancy.We conclude that transcription-coupled recruitment of CHD1 and CHD2 occurs at transcribed gene TSSs and at intragenic and intergenic enhancer-like sites.The recruitment of CHD1 and CHD2 regulates the architecture of active chromatin regions through chromatin accessibility and nucleosome disassembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Nutrition, NOVUM, Karolinska Institutet, Huddinge, 141 83 Sweden.

ABSTRACT

Background: CHD1 and CHD2 chromatin remodeling enzymes play important roles in development, cancer and differentiation. At a molecular level, the mechanisms are not fully understood but include transcriptional regulation, nucleosome organization and turnover.

Results: Here we show human CHD1 and CHD2 enzymes co-occupy active chromatin regions associated with transcription start sites (TSS), enhancer like regions and active tRNA genes. We demonstrate that their recruitment is transcription-coupled. CHD1 and CHD2 show distinct binding profiles across active TSS regions. Depletion of CHD1 influences chromatin accessibility at TSS and enhancer-like chromatin regions. CHD2 depletion causes increased histone H3 and reduced histone variant H3.3 occupancy.

Conclusions: We conclude that transcription-coupled recruitment of CHD1 and CHD2 occurs at transcribed gene TSSs and at intragenic and intergenic enhancer-like sites. The recruitment of CHD1 and CHD2 regulates the architecture of active chromatin regions through chromatin accessibility and nucleosome disassembly.

No MeSH data available.


Related in: MedlinePlus

CHD1 and CHD2 are enriched at an enhancer-like chromatin state with RNA polymerase II (Pol II). (A)The occupancy of CHD1 and CHD2 occurs primarily at enhancer-like chromatin state 4, which also showed the strongest binding by Pol II (Kruskall-Wallis test with Dunn’s post test correction, k = 3, P <0.0001, comparing enhancer state 4 to all other enhancer-like chromatin states). (B) In contrast H3K4 methylation was observed to different extents at all enhancer-like chromatin states.
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Fig3: CHD1 and CHD2 are enriched at an enhancer-like chromatin state with RNA polymerase II (Pol II). (A)The occupancy of CHD1 and CHD2 occurs primarily at enhancer-like chromatin state 4, which also showed the strongest binding by Pol II (Kruskall-Wallis test with Dunn’s post test correction, k = 3, P <0.0001, comparing enhancer state 4 to all other enhancer-like chromatin states). (B) In contrast H3K4 methylation was observed to different extents at all enhancer-like chromatin states.

Mentions: Another chromatin state strongly associated with CHD1 or CHD2 enrichment was enhancer chromatin state 4 (Figure 3A). The enhancer chromatin states defined by Ernst et al. were identified through combinations of H3K4-methylation including the enhancer-specific H3K4me1 and histone acetylation (Table 1, Figure 3B). We found that enhancer state 4, which is distinguished by higher H3K4me3 and H3K9/27 ac than other enhancer states, was associated with Pol II, CHD1 and CHD2 enrichment. Other enhancer chromatin states 5 to 7, defined by lower levels of H3K4 methylation and H3K9/27 ac, showed weaker enrichment for Pol II, CHD1 and CHD2. This suggested that transcription of enhancers is coupled to chromatin remodeling by CHD1 and CHD2. Furthermore it has been demonstrated that a fraction of Pol II binding sites overlap with a distinct set of RNA polymerase III binding sites including active tRNA genes [34, 35]. Such active tRNA genes are bound by BRF1, the transcription factor IIIB subunit [36]. Consistent with this, we found CHD1 and CHD2 were enriched at BRF1 but not at the alternate Pol III transcription factor, BRF2 binding sites in K562 cells (see Additional file 2). In this scenario, BRF2 binding sites function as control Pol III sites that do not overlap with Pol II binding. This suggests CHD1 and CHD2 may function at a subset of Pol III genes where Pol II transcription occurs, such as tRNAs.Figure 3


Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin accessibility and histone H3 and H3.3 occupancy at active chromatin regions.

Siggens L, Cordeddu L, Rönnerblad M, Lennartsson A, Ekwall K - Epigenetics Chromatin (2015)

CHD1 and CHD2 are enriched at an enhancer-like chromatin state with RNA polymerase II (Pol II). (A)The occupancy of CHD1 and CHD2 occurs primarily at enhancer-like chromatin state 4, which also showed the strongest binding by Pol II (Kruskall-Wallis test with Dunn’s post test correction, k = 3, P <0.0001, comparing enhancer state 4 to all other enhancer-like chromatin states). (B) In contrast H3K4 methylation was observed to different extents at all enhancer-like chromatin states.
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Related In: Results  -  Collection

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Fig3: CHD1 and CHD2 are enriched at an enhancer-like chromatin state with RNA polymerase II (Pol II). (A)The occupancy of CHD1 and CHD2 occurs primarily at enhancer-like chromatin state 4, which also showed the strongest binding by Pol II (Kruskall-Wallis test with Dunn’s post test correction, k = 3, P <0.0001, comparing enhancer state 4 to all other enhancer-like chromatin states). (B) In contrast H3K4 methylation was observed to different extents at all enhancer-like chromatin states.
Mentions: Another chromatin state strongly associated with CHD1 or CHD2 enrichment was enhancer chromatin state 4 (Figure 3A). The enhancer chromatin states defined by Ernst et al. were identified through combinations of H3K4-methylation including the enhancer-specific H3K4me1 and histone acetylation (Table 1, Figure 3B). We found that enhancer state 4, which is distinguished by higher H3K4me3 and H3K9/27 ac than other enhancer states, was associated with Pol II, CHD1 and CHD2 enrichment. Other enhancer chromatin states 5 to 7, defined by lower levels of H3K4 methylation and H3K9/27 ac, showed weaker enrichment for Pol II, CHD1 and CHD2. This suggested that transcription of enhancers is coupled to chromatin remodeling by CHD1 and CHD2. Furthermore it has been demonstrated that a fraction of Pol II binding sites overlap with a distinct set of RNA polymerase III binding sites including active tRNA genes [34, 35]. Such active tRNA genes are bound by BRF1, the transcription factor IIIB subunit [36]. Consistent with this, we found CHD1 and CHD2 were enriched at BRF1 but not at the alternate Pol III transcription factor, BRF2 binding sites in K562 cells (see Additional file 2). In this scenario, BRF2 binding sites function as control Pol III sites that do not overlap with Pol II binding. This suggests CHD1 and CHD2 may function at a subset of Pol III genes where Pol II transcription occurs, such as tRNAs.Figure 3

Bottom Line: CHD2 depletion causes increased histone H3 and reduced histone variant H3.3 occupancy.We conclude that transcription-coupled recruitment of CHD1 and CHD2 occurs at transcribed gene TSSs and at intragenic and intergenic enhancer-like sites.The recruitment of CHD1 and CHD2 regulates the architecture of active chromatin regions through chromatin accessibility and nucleosome disassembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Nutrition, NOVUM, Karolinska Institutet, Huddinge, 141 83 Sweden.

ABSTRACT

Background: CHD1 and CHD2 chromatin remodeling enzymes play important roles in development, cancer and differentiation. At a molecular level, the mechanisms are not fully understood but include transcriptional regulation, nucleosome organization and turnover.

Results: Here we show human CHD1 and CHD2 enzymes co-occupy active chromatin regions associated with transcription start sites (TSS), enhancer like regions and active tRNA genes. We demonstrate that their recruitment is transcription-coupled. CHD1 and CHD2 show distinct binding profiles across active TSS regions. Depletion of CHD1 influences chromatin accessibility at TSS and enhancer-like chromatin regions. CHD2 depletion causes increased histone H3 and reduced histone variant H3.3 occupancy.

Conclusions: We conclude that transcription-coupled recruitment of CHD1 and CHD2 occurs at transcribed gene TSSs and at intragenic and intergenic enhancer-like sites. The recruitment of CHD1 and CHD2 regulates the architecture of active chromatin regions through chromatin accessibility and nucleosome disassembly.

No MeSH data available.


Related in: MedlinePlus