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.
Highlights
Polycomb group (PcG) proteins are evolutionarily conserved epigenetic repressors of developmental genes
Taking advantage of a Pcgf6 conditional allele, we show that PCGF6 and RING1B common targets are enriched for meiosis- and germ cell-related genes in embryonic stem cells (ESCs), and that such genes are robustly de-repressed in the absence of PCGF6 (Pcgf6-KO)
We confirmed EZH2 or SET1 were not co-IPed with either FLAG-PCGF6 or FLAG-RING1B. These results suggested that PCGF6 would be primarily involved in non-canonical polycomb repressive complexes 1 (PRC1), PCGF6-PRC1, in mouse ESCs
Summary
Polycomb group (PcG) proteins are evolutionarily conserved epigenetic repressors of developmental genes. Canonical PRC1 (cPRC1) may include PCGF2 ( known as MEL18: melanoma nuclear protein 18) or PCGF4 ( known as Bmi: B cell-specific Moloney murine leukemia virus integration site 1). These cPRC1 complexes can be further classified into specific sub-complexes according to their association with CBX (CBX2/4/6/7/8) or PHC (PHC1/2/3: polyhomeotic homologs 1, 2 and 3) (Gao et al, 2012; Vandamme et al, 2011). CBX proteins contribute to recognition of H3K27me, and mediate recruitment of cPRC1 into target loci; while PHC proteins mediate gene compaction through polymerization of the SAM (sterile alpha motif) domain to facilitate transcriptional silencing (Isono et al, 2013)
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