Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment
- PMID: 24857660
- PMCID: PMC4062935
- DOI: 10.1016/j.celrep.2014.04.012
Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment
Abstract
The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs), CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Figures








Similar articles
-
Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.Nat Commun. 2016 Nov 28;7:13661. doi: 10.1038/ncomms13661. Nat Commun. 2016. PMID: 27892467 Free PMC article.
-
Polycomb-like proteins link the PRC2 complex to CpG islands.Nature. 2017 Sep 14;549(7671):287-291. doi: 10.1038/nature23881. Epub 2017 Sep 6. Nature. 2017. PMID: 28869966 Free PMC article.
-
PRC1 and PRC2 are not required for targeting of H2A.Z to developmental genes in embryonic stem cells.PLoS One. 2012;7(4):e34848. doi: 10.1371/journal.pone.0034848. Epub 2012 Apr 9. PLoS One. 2012. PMID: 22496869 Free PMC article.
-
Polycomb Gene Silencing Mechanisms: PRC2 Chromatin Targeting, H3K27me3 'Readout', and Phase Separation-Based Compaction.Trends Genet. 2021 Jun;37(6):547-565. doi: 10.1016/j.tig.2020.12.006. Epub 2021 Jan 22. Trends Genet. 2021. PMID: 33494958 Free PMC article. Review.
-
Polycomb repressive complex 2 in embryonic stem cells: an overview.Protein Cell. 2010 Dec;1(12):1056-62. doi: 10.1007/s13238-010-0142-7. Epub 2011 Jan 8. Protein Cell. 2010. PMID: 21213100 Free PMC article. Review.
Cited by
-
Polycomb genes, miRNA, and their deregulation in B-cell malignancies.Blood. 2015 Feb 19;125(8):1217-25. doi: 10.1182/blood-2014-10-606822. Epub 2015 Jan 7. Blood. 2015. PMID: 25568352 Free PMC article. Review.
-
Chromatin signaling in muscle stem cells: interpreting the regenerative microenvironment.Front Aging Neurosci. 2015 Apr 7;7:36. doi: 10.3389/fnagi.2015.00036. eCollection 2015. Front Aging Neurosci. 2015. PMID: 25904863 Free PMC article. Review.
-
Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets polycomb Cbx7-PRC1 to chromatin.Elife. 2016 Oct 10;5:e17667. doi: 10.7554/eLife.17667. Elife. 2016. PMID: 27723458 Free PMC article.
-
Context-specific Polycomb mechanisms in development.Nat Rev Genet. 2022 Nov;23(11):680-695. doi: 10.1038/s41576-022-00499-0. Epub 2022 Jun 9. Nat Rev Genet. 2022. PMID: 35681061 Free PMC article. Review.
-
Loss of the Polycomb group protein Rnf2 results in derepression of tbx-transcription factors and defects in embryonic and cardiac development.Sci Rep. 2019 Mar 13;9(1):4327. doi: 10.1038/s41598-019-40867-1. Sci Rep. 2019. PMID: 30867528 Free PMC article.
References
-
- Atsuta T., Fujimura S., Moriya H., Vidal M., Akasaka T., Koseki H. Production of monoclonal antibodies against mammalian Ring1B proteins. Hybridoma. 2001;20:43–46. - PubMed
-
- Bestor T.H. The DNA methyltransferases of mammals. Hum. Mol. Genet. 2000;9:2395–2402. - PubMed
-
- Bezsonova I., Walker J.R., Bacik J.P., Duan S., Dhe-Paganon S., Arrowsmith C.H. Ring1B contains a ubiquitin-like docking module for interaction with Cbx proteins. Biochemistry. 2009;48:10542–10548. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- BBS/E/B/0000L748/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
- G1000902/MRC_/Medical Research Council/United Kingdom
- MC_EX_UU_G1000902/MRC_/Medical Research Council/United Kingdom
- BBS/E/B/0000H234/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
- MC_EX_G1000902/MRC_/Medical Research Council/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources