Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Open accessAbstract
The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mouse ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox gene clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox gene network. In contrast, promoter-enhancer contacts are maintained in the absence of Polycomb repression, with accompanying widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional upregulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that the selective release of genes from this spatial network underlies cell fate specification during early embryonic development.
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Knockouts of both PRC1 and PRC2 components affect chromosomal contacts between Polycomb-bound loci.
“However, knockouts of both PRC1 and PRC2 components affect chromosomal contacts between Polycomb-bound loci [280, 360].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [280]
Contacts between promoters of Hox genes in ESCs (in which they are inactive) depend on Polycomb Repressive complex 1.
“contacts between the promoters of Hox genes in ESCs (in which they are inactive) that were shown to depend on Polycomb Repressive complex 1 [280].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [280]
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- Authors
- Schoenfelder, S., Sugar, R., Dimond, A., Javierre, B.-M., Armstrong, H., Mifsud, B., Dimitrova, E., Matheson, L., Tavares-Cadete, F., Furlan-Magaril, M., Segonds-Pichon, A., Jurkowski, W., Wingett, S. W., Tabbada, K., Andrews, S., Herman, B., LeProust, E., Osborne, C. S., Koseki, H., Fraser, P., Luscombe, N. M., & Elderkin, S.
- Affiliations
- Babraham Institute (GB)
- European Bioinformatics Institute (GB)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Agilent Technologies (United States) (US)
- RIKEN Center for Integrative Medical Sciences (JP)
- Corresponding author
- Elderkin, Sarah
- ORCID
- Venue
- Nature Genetics
- Published
- 2015-08-31
- Volume
- 47
- Issue
- 10
- Pages
- 1179-1186
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC4847639
- OpenAlex
- W2243544746
- Cited by
- 398
- References
- 9
- Citations by year
- 2026: 25 · 2025: 14 · 2024: 26 · 2023: 25 · 2022: 34 · 2021: 52 · 2020: 48 · 2019: 47 · 2018: 39 · 2017: 43 · 2016: 36 · 2015: 8
- FWCI
- 18.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (085102, WT085102MA, 093606)
- Francis Crick Institute (10110)
- Cancer Research UK (16358, A16358)
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405, BBS/E/B/0000L748, BBS/E/B/000C0404, BBS/E/B/0000H234, BBS/E/T/000PR5885, BBS/E/T/000PR6193)
- Japan Society for the Promotion of Science (23249015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- PRC1, polycomb repressive complex 2, mouse embryonic stem cells, 3D genome organization, chromatin structure, Hox gene clusters, poised enhancers, Polycomb repression, cell fate specification, pluripotency, chromatin accessibility
- MeSH terms
- Animals, Promoter Regions, Genetic, Genome, Mice, Embryonic Stem Cells, Polycomb-Group Proteins
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