Dot1pは,核細胞核のメチル化により,酵母における静音化を調節する
Fred van Leeuwen1, Philip R Gafken, Daniel E Gottschling
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cell
|June 28, 2002
まとめ
ドット1タンパク質はヒストンH3をメチル化し,ライシン79,重要なエピジェネティックマークである. このメチル化は,クロマチンの遺伝子サイレンシングを維持するために不可欠であり,酵母におけるテロメアサイレンシングに影響を与えます.
科学分野:
- エピジェネティクスと分子生物学
- クロマチン生物学 クロマチン生物学
- イースト遺伝学 イースト遺伝学
背景:
- セカロマイセス・セレヴィシア (酵母菌) のテロメア静音化は,よく研究された現象です.
- DOT1遺伝子は,この静音化プロセスにおけるその役割のために最初に特定されました.
- ヒストンの改変は,遺伝子発現とクロマチンの構造の重要な調節因子である.
研究 の 目的:
- DOT1遺伝子産物の分子機能を明らかにするために,Dot1p.
- Dot1p.によって触媒化された特定のヒストンの改変を特定する.
- テロメア静音化とクロマチンの調節におけるこの変化の役割を理解するために.
主な方法:
- Dot1pの酵素活性を決定する生化学的分析.
- タンパク質の局所化を評価するためにクロマチン免疫降水 (ChIP) を用いる.
- ワイルドタイプおよびドット1デルタ酵母菌株における遺伝子静止とタンパク質分布の分析.
主要な成果:
- Dot1pは,ヒストンH3をライシン79 (H3K79メチル化) に特異的にメチル化することが判明しました.
- このメチル化は,組み立てられたクロマチンの文脈で起こります.
- Dot1pは,H3K79のメチル化にインビボで主たる酵素であり,ヒストンH3.3の約90%に影響する.
- Dot1p機能 (dot1delta) の喪失は,静音化を損ない,静音化タンパク質の分布を変化させます.
結論:
- ドット1pによるヒストンH3ライシン79メチル化は,適切なテロメア静音化に不可欠です.
- H3K79メチル化は,静止タンパク質 (Sirタンパク質など) が他のゲノム領域に結合するのを防ぐことによって,静止を特定の位置に制限する可能性がある.
- Dot1pとヒストンH3の保存された性質は,他の真核生物でも同様の表遺伝子調節機構が機能することを示唆しています.
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