Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells
Abstract Background The hierarchical organization of eukaryotic chromatin plays a central role in gene regulation, by controlling the extent to which the transcription machinery can access DNA. The histone variants H3.3 and H2A.Z have recently been identified as key regulatory players in this proces...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Biology |
| Online Access: | http://link.springer.com/article/10.1186/s12915-018-0568-6 |
| _version_ | 1818410683502428160 |
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| author | Yan Wang Haizhen Long Juan Yu Liping Dong Michel Wassef Baowen Zhuo Xia Li Jicheng Zhao Min Wang Cuifang Liu Zengqi Wen Luyuan Chang Ping Chen Qian-fei Wang Xueqing Xu Raphael Margueron Guohong Li |
| author_facet | Yan Wang Haizhen Long Juan Yu Liping Dong Michel Wassef Baowen Zhuo Xia Li Jicheng Zhao Min Wang Cuifang Liu Zengqi Wen Luyuan Chang Ping Chen Qian-fei Wang Xueqing Xu Raphael Margueron Guohong Li |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Abstract Background The hierarchical organization of eukaryotic chromatin plays a central role in gene regulation, by controlling the extent to which the transcription machinery can access DNA. The histone variants H3.3 and H2A.Z have recently been identified as key regulatory players in this process, but the underlying molecular mechanisms by which they permit or restrict gene expression remain unclear. Here, we investigated the regulatory function of H3.3 and H2A.Z on chromatin dynamics and Polycomb-mediated gene silencing. Results Our ChIP-seq analysis reveals that in mouse embryonic stem (mES) cells, H3K27me3 enrichment correlates strongly with H2A.Z. We further demonstrate that H2A.Z promotes PRC2 activity on H3K27 methylation through facilitating chromatin compaction both in vitro and in mES cells. In contrast, PRC2 activity is counteracted by H3.3 through impairing chromatin compaction. However, a subset of H3.3 may positively regulate PRC2-dependent H3K27 methylation via coordinating depositions of H2A.Z to developmental and signaling genes in mES cells. Using all-trans retinoic acid (tRA)-induced gene as a model, we show that the dynamic deposition of H2A.Z and H3.3 coordinately regulates the PRC2-dependent H3K27 methylation by modulating local chromatin structure at the promoter region during the process of turning genes off. Conclusions Our study provides key insights into the mechanism of how histone variants H3.3 and H2A.Z function coordinately to finely tune the PRC2 enzymatic activity during gene silencing, through promoting or impairing chromosome compaction respectively. |
| first_indexed | 2024-12-14T10:19:25Z |
| format | Article |
| id | doaj.art-9bcdce8575f142c6ade14220a178e71e |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-14T10:19:25Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-9bcdce8575f142c6ade14220a178e71e2022-12-21T23:06:39ZengBMCBMC Biology1741-70072018-09-0116111810.1186/s12915-018-0568-6Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cellsYan Wang0Haizhen Long1Juan Yu2Liping Dong3Michel Wassef4Baowen Zhuo5Xia Li6Jicheng Zhao7Min Wang8Cuifang Liu9Zengqi Wen10Luyuan Chang11Ping Chen12Qian-fei Wang13Xueqing Xu14Raphael Margueron15Guohong Li16National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesInstitut Curie, PSL Research University, INSERM U934, CNRS UMR3215Baoan Maternal and Child Health Hospital, Jinan UniversityKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of SciencesBaoan Maternal and Child Health Hospital, Jinan UniversityInstitut Curie, PSL Research University, INSERM U934, CNRS UMR3215National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesAbstract Background The hierarchical organization of eukaryotic chromatin plays a central role in gene regulation, by controlling the extent to which the transcription machinery can access DNA. The histone variants H3.3 and H2A.Z have recently been identified as key regulatory players in this process, but the underlying molecular mechanisms by which they permit or restrict gene expression remain unclear. Here, we investigated the regulatory function of H3.3 and H2A.Z on chromatin dynamics and Polycomb-mediated gene silencing. Results Our ChIP-seq analysis reveals that in mouse embryonic stem (mES) cells, H3K27me3 enrichment correlates strongly with H2A.Z. We further demonstrate that H2A.Z promotes PRC2 activity on H3K27 methylation through facilitating chromatin compaction both in vitro and in mES cells. In contrast, PRC2 activity is counteracted by H3.3 through impairing chromatin compaction. However, a subset of H3.3 may positively regulate PRC2-dependent H3K27 methylation via coordinating depositions of H2A.Z to developmental and signaling genes in mES cells. Using all-trans retinoic acid (tRA)-induced gene as a model, we show that the dynamic deposition of H2A.Z and H3.3 coordinately regulates the PRC2-dependent H3K27 methylation by modulating local chromatin structure at the promoter region during the process of turning genes off. Conclusions Our study provides key insights into the mechanism of how histone variants H3.3 and H2A.Z function coordinately to finely tune the PRC2 enzymatic activity during gene silencing, through promoting or impairing chromosome compaction respectively.http://link.springer.com/article/10.1186/s12915-018-0568-6 |
| spellingShingle | Yan Wang Haizhen Long Juan Yu Liping Dong Michel Wassef Baowen Zhuo Xia Li Jicheng Zhao Min Wang Cuifang Liu Zengqi Wen Luyuan Chang Ping Chen Qian-fei Wang Xueqing Xu Raphael Margueron Guohong Li Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells BMC Biology |
| title | Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells |
| title_full | Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells |
| title_fullStr | Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells |
| title_full_unstemmed | Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells |
| title_short | Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells |
| title_sort | histone variants h2a z and h3 3 coordinately regulate prc2 dependent h3k27me3 deposition and gene expression regulation in mes cells |
| url | http://link.springer.com/article/10.1186/s12915-018-0568-6 |
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