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Elife ; 62017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28304275

RESUMO

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.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/fisiologia , Regulação da Expressão Gênica , Complexo Repressor Polycomb 1/metabolismo , Animais , Inativação Gênica , Histonas/metabolismo , Camundongos , Ubiquitina-Proteína Ligases/metabolismo
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