ES細胞酸塩の仕様におけるDpy-30の役割は,二価ドメイン内のH3K4メチル化の調節によるものです
Hao Jiang1, Abhijit Shukla, Xiaoling Wang
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, 10065, USA.
Cell
|February 22, 2011
まとめ
哺乳類のDpy-30タンパク質は,胚性幹細胞 (ESC) のヒストンH3K4トリメチル化 (H3K4me3) を調節する. Dpy-30の枯渇は,ESCの分化,特に神経系統の発達を阻害し,発達の遺伝子調節におけるその役割を強調する.
科学分野:
- エピジェネティクス エピジェネティクス
- クロマチンの生物学
- 発達生物学 発達生物学とは
背景:
- ヒストンH3K4メチル化 (H3K4me) は,活性遺伝子をマークする.
- 二対性染色体マーク (H3K4meとH3K27me) は,胚性幹細胞 (ESC) のバランスの取れた発達遺伝子を特徴付けています.
- ESCの維持と分化におけるH3K4メチル化の正確な機能は不明である.
研究 の 目的:
- H3K4メチル化におけるSET1/MLLヒストンメチルトランスフェラーゼ複合体のサブユニットである哺乳類のDpy-30の役割を調査する.
- ESCの自己再生と分化におけるDpy-30とH3K4メチル化の機能的重要性を決定する.
主な方法:
- Dpy-30.0によるH3K4メチル化の試験管内調節.
- Dpy-30の枯渇時に染色体H3K4トリメチル化 (H3K4me3) の全ゲノム分析.
- ESCの自己更新と差別化の可能性の評価,特に神経系へ向けて.
主要な成果:
- Dpy-30はH3K4メチル化をインビトロで調節し,H3K4me3をゲノム全体で調節する.
- Dpy-30の枯渇はESCの自己更新に影響はしませんが,特に神経の分化,特に神経の分化を著しく阻害します.
- 遺伝子誘導とH3K4me3の発達部位における欠陥は,分化障害に伴います.
結論:
- Dpy-30は,H3K4me3を調節するために不可欠であり,双価クロマチンのマークの重要な構成要素です.
- Dpy-30経由のSET1/MLL複合物媒介によるH3K4メチル化は,ESC運命移行中の発達遺伝子調節において重要な役割を果たします.
- この研究は,ESCの差異化可能性を制御するDpy-30の機能的な役割を確立しています.
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