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)].
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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- Cell Biology
The oviduct is the site of fertilization and preimplantation embryo development in mammals. Evidence suggests that gametes alter oviductal gene expression. To delineate the adaptive interactions between the oviduct and gamete/embryo, we performed a multi-omics characterization of oviductal tissues utilizing bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and proteomics collected from distal and proximal at various stages after mating in mice. We observed robust region-specific transcriptional signatures. Specifically, the presence of sperm induces genes involved in pro-inflammatory responses in the proximal region at 0.5 days post-coitus (dpc). Genes involved in inflammatory responses were produced specifically by secretory epithelial cells in the oviduct. At 1.5 and 2.5 dpc, genes involved in pyruvate and glycolysis were enriched in the proximal region, potentially providing metabolic support for developing embryos. Abundant proteins in the oviductal fluid were differentially observed between naturally fertilized and superovulated samples. RNA-seq data were used to identify transcription factors predicted to influence protein abundance in the proteomic data via a novel machine learning model based on transformers of integrating transcriptomics and proteomics data. The transformers identified influential transcription factors and correlated predictive protein expressions in alignment with the in vivo-derived data. Lastly, we found some differences between inflammatory responses in sperm-exposed mouse oviducts compared to hydrosalpinx Fallopian tubes from patients. In conclusion, our multi-omics characterization and subsequent in vivo confirmation of proteins/RNAs indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner.
