PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes
- RIKEN Center for Integrative Medical Sciences, Japan
- Faculty of Medical Sciences, Kyushu University, Japan
- Oxford University, United Kingdom
- Kazusa DNA Research Institute, Japan
- University of Oxford, United Kingdom
- National University of Singapore, Singapore
- Saitama Medical University, Japan
- Faculty of Medical Sciences, Kyushu University, United Kingdom
Abstract
The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.
Data availability
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PCGF6-PRC1 suppresses premature differentiation of embryonic stem cells by silencing germ cell-related genes [RNA-Seq]Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE84480).
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PCGF6-PRC1 suppresses premature differentiation of embryonic stem cells by silencing germ cell-related genes [ChIP-Seq]Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87484).
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Cbx7_ChIPSeqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1041373).
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Max_ChIPSeqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1171650).
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BioMyc_ChIPSeqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1171648).
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KDM2Bfl/fl_RING1B_ChIPSeqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE55698).
Article and author information
Author details
Funding
RIKEN
- Haruhiko Koseki
Ministry of Education, Culture, Sports, Science, and Technology
- Haruhiko Koseki
Japan Science and Technology Agency (Strategic Basic Research Programs)
- Haruhiko Koseki
Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research on Innovative Areas (#26112516))
- Mitsuhiro Endoh
Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Young Scientist (B) (#25871129))
- Mitsuhiro Endoh
Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research (C) (#16K07372))
- Mitsuhiro Endoh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were carried out according to the in-house guidelines for the care and use of laboratory animals of the RIKEN Center for Integrative Medical Sciences, Yokohama, Japan [Approval number: Kei-27-001(7)].
Reviewing Editor
- Robb Krumlauf, Stowers Institute for Medical Research, United States
Version history
- Received: September 1, 2016
- Accepted: March 15, 2017
- Accepted Manuscript published: March 17, 2017 (version 1)
- Version of Record published: March 31, 2017 (version 2)
- Version of Record updated: April 25, 2017 (version 3)
Copyright
© 2017, Endoh 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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PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes
eLife 6:e21064.
https://doi.org/10.7554/eLife.21064
Further reading
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