H2AZは,ES細胞のポリコンブ複合標的遺伝子に濃縮され,系統のコミットメントに必要なものです

Menno P Creyghton¹, Styliani Markoulaki, Stuart S Levine

¹Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.

Cell

|November 11, 2008

まとめ

ヒストン変種H2AZは哺乳類の発達に不可欠であり,ポリコンブ群のタンパク質とともに遺伝子発現と細胞分化を調節する. そのダイナミックな再分布は,細胞運命を変化させるための鍵です.

科学分野:

エピジェネティクスと発達生物学
クロマチンの生物学
遺伝子規制遺伝子規制

背景:

クロマチンの構造は,遺伝子発現と細胞運命を決定することに大きく影響します.
ヒストン変異体H2AZは染色体機能に関与し,哺乳類の発達において重要な,しかし定義されていない役割を果たしている.

研究の目的:

哺乳類の発達におけるH2AZの役割と,ポリコンブ群 (PcG) のタンパク質との関係を調査する.
H2AZが発達中の遺伝子発現と細胞の分化にどのように影響するか解明する.

主な方法:

遺伝子プロモーターのH2AZ占有率をマッピングするための全ゲノム分析.
RNA干渉 (RNAi) は,H2AZが遺伝子発現に及ぼす機能的影響を評価する.
標的遺伝子プロモーターにおけるH2AZとPcGタンパク質の相互依存性の分析.

主要な成果:

H2AZは,PcGタンパク質Suz12と類似した,発達的に重要な遺伝子のプロモーターを占有しています.
H2AZは標的遺伝子発現の調節に不可欠であり,プロモーターのPcGタンパク質と相互依存しています.
H2AZは胚性幹細胞 (ES) の分化に必要であり,系統にコミットした細胞で動的に再分布する.

結論:

H2AZは,PcGタンパク質と結合して,ES細胞の特殊なクロマチンの状態を確立します.
H2AZのダイナミックな再配分は,発達の遺伝子発現プログラムを実行し,細胞運命の移行を促進するために不可欠です.

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