ISWIクロマチンリモデラーは,基板の偏好を決定するために,核細胞変異を感知する

Geoffrey P Dann¹, Glen P Liszczak¹, John D Bagert¹

¹Department of Chemistry, Princeton University, Frick Laboratory, Princeton, New Jersey 08544, USA.

Nature

|August 3, 2017

まとめ

クロマチンの改造機は付属サブユニットを用いて改造された核細胞を標的にします核細胞酸パッチは,調整可能な相互作用サイトとして機能し,リモデラーの活動に不可欠です.

科学分野:

分子生物学
エピジェネティクス
クロマチン生物学

背景:

ATPに依存するクロマチンのリモデラーは,ニュクレオソームの位置を変えることで,遺伝子のアクセシビリティを制御する.
これらのリモデラーが特定の核細胞基板を選択するメカニズムは不明である.
リモデラーの保存されたタンパク質ドメインは,しばしば核細胞特異と相互作用する.

研究の目的:

ヒトISWIファミリーの染色体リモデラーが改変された核細胞基板を区別する方法を調査する.
リモデラー活性を調節する酸性パッチのような核細胞変異と特定の領域の役割を特定する.

主な方法:

DNAバーコードのモノヌクレソームライブラリを使用した定量的な高通量法を使用した.
ISWIリモデラーの生化学的活性を様々な核細胞変異に対してプロファイリングした.

主要な成果:

ISWIリモデラーのアクセサリーサブユニットは,差異的に改変された核細胞を区別し,それに応じて活動を指示します.
核細胞酸パッチは,ISWI,CHD,SWI/SNFリモデラーの最大限の活動に不可欠です.
酸性パッチの近くの改変はリモデラーの活動を調節し,調節可能な相互作用ホットスポットとしての役割を強調します.

結論:

ヌクレオソームの改変状態は,付属サブユニットを介してクロマチンのリモデラー標的化に影響を与えます.
核酸パッチはATP依存の染色体リモデラー機能の一般的な要件である.
酸性パッチは,クロマチンエフェクターにとって重要な調整可能な相互作用部位として機能する.

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