PCGF3/5-PRC1は,X染色体不活性化におけるポリコンブ募集を開始する

Mafalda Almeida¹, Greta Pintacuda¹, Osamu Masui²

¹Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.

Science (New York, N.Y.)

|June 10, 2017

まとめ

非正規のポリコンブ群のRING finger 3/5 (PCGF3/5) -PRC1複合体は,遺伝子静止と胚の発達に不可欠なXist RNAによるポリコンブ抑制複合体の募集を開始する.

科学分野:

エピジェネティクス
分子生物学
遺伝学

背景:

Xist RNAのような長い非コードRNAはクロマチンを調節する.
ポリコンブ抑制複合体 (PRC1とPRC2) は重要な表遺伝子調節体である.
Xist RNAはPRC1とPRC2を遺伝子サイレンスに採用する.

研究の目的:

Xist RNAによるPRC1とPRC2の初期徴募メカニズムを調査する.
Xist媒介の遺伝子抑制における非正規のポリコンブ複合体の役割を解明する.

主な方法:

遺伝子ノックアウト研究 (Pcgf3/5)
ヒストンの改変分析 (H2A全存在化,H3K27メチル化)
Xist RNAによる遺伝子抑制の分析

主要な成果:

非正規のPCGF3/5-PRC1複合体は,Xist RNAによってPRC1とPRC2のリクルートを開始する.
PCGF3/5-PRC1媒介によるH2AK119の普及は,さらなるPRCの採用を示唆している.
Pcgf3 / 5 ノックアウトは胚の死亡を引き起こし,Xist媒介の遺伝子静止を廃止します.

結論:

PCGF3/5-PRC1複合体は,XistRNA媒介によるポリコンブ募集と遺伝子静止に不可欠である.
ヒストンH2AK119のユビキティレーションは,ポリコンブ領域の形成を vivo で開始する.
発見は,Xist RNAによるポリコンブ募集の既存のモデルに異議を唱える.

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