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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Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of matrix remodeling associated 5b (mxra5b), matrilin1 (matn1), and the transcription factor kruppel-like factor 2a (klf2a), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.
