RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes
- University of Oxford, United Kingdom
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.
Data availability
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RBYP stimulates PRC1 to shape chromatin-based communication between polycomb repressive complexesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE83135).
Article and author information
Author details
Funding
European Research Council (Consolidator grant, 681440)
- Robert J Klose
Wellcome (Senior Research Fellowship, 098024/Z/11/Z)
- Robert J Klose
Lister Institute of Preventive Medicine
- Robert J Klose
Wellcome (097813/Z/11/Z)
- Benedikt M Kessler
John Fell Fund, University of Oxford (133/075)
- Benedikt M Kessler
Kennedy Memorial Trust
- Benedikt M Kessler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Rose et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes
eLife 5:e18591.
https://doi.org/10.7554/eLife.18591
