Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation.

Autor:	Blackledge NP; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Farcas AM; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Kondo T; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., King HW; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., McGouran JF; Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK., Hanssen LLP; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Ito S; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Cooper S; Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Kondo K; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Koseki Y; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Ishikura T; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Long HK; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Sheahan TW; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Brockdorff N; Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK., Kessler BM; Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK., Koseki H; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan., Klose RJ; Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: rob.klose@bioch.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2014 Jun 05; Vol. 157 (6), pp. 1445-1459. Date of Electronic Publication: 2014 May 22.
DOI:	10.1016/j.cell.2014.05.004
Abstrakt:	Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2 occupancy at target sites in vivo. (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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