CpG Islands Shape the Epigenome Landscape

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Papin, Christophe¹  Le Gras, Stephanie¹  Ibrahim, Abdulkhaleg^1,2  Salem, Hatem^1,2  Karimi, Mohammad Mahdi³  Stoll, Isabelle¹  Ugrinova, Iva⁴  Schroder, Maria⁴  Fontaine-Pelletier, Emeline⁵  Omran, Ziad⁶  Bronner, Christian¹  Dimitrov, Stefan^4,5  Hamiche, Ali^1,2 

[1] Equipe Labellisde Ligue Canc, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire IGBM,UdS, 1 Rue Laurent Fries,BP 10142, F-67404 Illkirch Graffenstaden, France

[2] Biotechnol Res Ctr BTRC, Tripoli, Libya

[3] Kings Coll London, Fac Life Sci & Med, Comprehens Canc Ctr, Sch Canc & Pharmaceut Sci, Denmark Hill, London, England

[4] Bulgarian Acad Sci, Roumen Tsanev Inst Mol Biol, Sofia, Bulgaria

[5] Univ Grenoble Alpes, Inst Adv Biosci, Inserm U 1209, CNRS UMR 5309, F-38000 Grenoble, France

[6] Umm AlQura Univ, Fac Pharm, Mecca, Saudi Arabia

关键词: histone variant H2A.Z;    nucleosome positioning;    transcription;    epigenetic modifications;    promoter chromatin organization;   

DOI  :  10.1016/j.jmb.2020.09.018

来源: Elsevier

【 摘 要 】

Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach. Our data reveal a clear correlation between CpG density, promoter activity and accumulation of active or repressive histone marks. CGI boundaries define the chromatin promoter regions that will be epigenetically modified. CpG-rich promoters are targeted by histone modifications and histone variants, while CpG-poor promoters are regulated by DNA methylation. CGIs boundaries, but not transcriptional activity, are essential determinants of H2A.Z positioning in vicinity of the promoters, suggesting that the presence of H2A.Z is not related to transcriptional control. Accordingly, H2A.Z depletion has no impact on gene expression of arrested mouse embryonic fibroblasts. Therefore, the underlying DNA sequence, the promoter CpG density and, to a lesser extent, transcriptional activity, are key factors implicated in promoter chromatin architecture. (C) 2020 The Author(s). Published by Elsevier Ltd.

【 授权许可】

Free