Regulation of preimplantation embryonic fate and plasticity by the PRC1 Polycomb group complex

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kumamoto University
• Principal Investigator: Endoh Mitsuhiro 熊本大学, 発生医学研究所, 助教 (40391883)
• Co-Investigator(Kenkyū-buntansha): 須田 年生 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エピジェネティクス / 発生 / 哺乳類 / 多能性幹細胞 / 転写 / 細胞分化

Outline of Final Research Achievements

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.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

ポリコーム群PRC1.6が他のPRC1とは異なり転写因子Mga/Maxに依存して標的遺伝子を認識すること、生殖関連遺伝子群および２細胞胚遺伝子群の新規エピジェネティック制御機構であることが明らかになった。グローバルなDNA脱メチル化を受けるナイーブ型の多能性幹細胞に特有のエピジェネティック機構であると考えられ、初期発生やエピジェネティックリプログラミングの分子基盤の理解に繋がる重要な発見と言える。