RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/18591 |
| _version_ | 1811180403577323520 |
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| author | Nathan R Rose Hamish W King Neil P Blackledge Nadezda A Fursova Katherine JI Ember Roman Fischer Benedikt M Kessler Robert J Klose |
| author_facet | Nathan R Rose Hamish W King Neil P Blackledge Nadezda A Fursova Katherine JI Ember Roman Fischer Benedikt M Kessler Robert J Klose |
| author_sort | Nathan R Rose |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:01:36Z |
| format | Article |
| id | doaj.art-479b684d7ad6400eb4b7ba915ba20c6e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:01:36Z |
| publishDate | 2016-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-479b684d7ad6400eb4b7ba915ba20c6e2022-12-22T04:32:45ZengeLife Sciences Publications LtdeLife2050-084X2016-10-01510.7554/eLife.18591RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexesNathan R Rose0Hamish W King1Neil P Blackledge2Nadezda A Fursova3Katherine JI Ember4Roman Fischer5https://orcid.org/0000-0002-9715-5951Benedikt M Kessler6Robert J Klose7https://orcid.org/0000-0002-8726-7888Department of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomTDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United KingdomTDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomPolycomb 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.https://elifesciences.org/articles/18591chromatingene expressionhistone modificationPolycomb repressive complexE3 ubiquitin ligase |
| spellingShingle | Nathan R Rose Hamish W King Neil P Blackledge Nadezda A Fursova Katherine JI Ember Roman Fischer Benedikt M Kessler Robert J Klose RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes eLife chromatin gene expression histone modification Polycomb repressive complex E3 ubiquitin ligase |
| title | RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes |
| title_full | RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes |
| title_fullStr | RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes |
| title_full_unstemmed | RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes |
| title_short | RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes |
| title_sort | rybp stimulates prc1 to shape chromatin based communication between polycomb repressive complexes |
| topic | chromatin gene expression histone modification Polycomb repressive complex E3 ubiquitin ligase |
| url | https://elifesciences.org/articles/18591 |
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