Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

Polycomb group (PcG) proteins are required for normal differentiation and development and are frequently deregulated in cancer. PcG proteins are involved in gene silencing; however, their role in initiation and maintenance of transcriptional repression is not well defined. Here, we show that knockou...

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Bibliographic Details
Published in:Molecular cell 2014-08, Vol.55 (3), p.347-360
Main Authors: Riising, Eva Madi, Comet, Itys, Leblanc, Benjamin, Wu, Xudong, Johansen, Jens Vilstrup, Helin, Kristian
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cell Differentiation - physiology
Cells, Cultured
CpG Islands
Dichlororibofuranosylbenzimidazole - pharmacology
Diterpenes - pharmacology
Embryonic Stem Cells - metabolism
Epigenesis, Genetic
Epoxy Compounds - pharmacology
Gene Expression Regulation, Developmental - drug effects
Gene Knockout Techniques
Gene Silencing - drug effects
Genome
Mice
Nucleosomes - genetics
Nucleosomes - metabolism
Phenanthrenes - pharmacology
Polycomb Repressive Complex 2 - metabolism
Protein Binding - genetics
Protein Binding - physiology
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Summary:Polycomb group (PcG) proteins are required for normal differentiation and development and are frequently deregulated in cancer. PcG proteins are involved in gene silencing; however, their role in initiation and maintenance of transcriptional repression is not well defined. Here, we show that knockout of the Polycomb repressive complex 2 (PRC2) does not lead to significant gene expression changes in mouse embryonic stem cells (mESCs) and that it is dispensable for initiating silencing of target genes during differentiation. Transcriptional inhibition in mESCs is sufficient to induce genome-wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of untranscribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity. [Display omitted] •PRC2 is dispensable for PcG target silencing in mouse embryonic stem cells•PRC2 is not required for initiation of gene repression during differentiation•Transcriptional inhibition leads to binding of PRC2 to CpG islands genome wide•PRC2 binding is inversely correlated to the nucleosome density of CpG islands Riising et al. report that PRC2 is not required to initiate repression of target genes during differentiation. Instead, gene silencing is sufficient to induce ectopic PRC2 recruitment to CpG islands and endogenous PcG target genes found in other tissues, suggesting that that the transcriptional state governs PRC2 binding.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2014.06.005