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RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes.

Abstract:
Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1(PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2(PRC2) which is required for normal histone H3 lysine 27 trimethylation(H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.7554/eLife.18591

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More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author


More from this funder
Funding agency for:
Klose, R
Grant:
098024/Z/11/Z
More from this funder
Funding agency for:
Klose, R
Grant:
098024/Z/11/Z
More from this funder
Funding agency for:
Kessler, B
Grant:
133/075
More from this funder
Funding agency for:
Kessler, B
Grant:
133/075
More from this funder
Funding agency for:
Kessler, B
Klose, R
Grant:
133/075
098024/Z/11/Z


Publisher:
eLife Sciences Publications
Journal:
eLife More from this journal
Publication date:
2016-10-05
Acceptance date:
2016-10-01
DOI:
EISSN:
2050-084X


Language:
English
Keywords:
Pubs id:
pubs:648298
UUID:
uuid:34ba0527-dfd1-42aa-9f2c-716c168d6bf3
Local pid:
pubs:648298
Source identifiers:
648298
Deposit date:
2016-10-07

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