不規則な地域は,凝縮とパートナー募集を通じてcBAFの活動を制御する

Ajinkya Patil¹, Amy R Strom², Joao A Paulo³

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.

Cell

|October 3, 2023

まとめ

染色体リモデレータの内在的に乱れた領域 (IDR) は,明確な配列規則を持っています. これらの規則はタンパク質の凝縮とパートナー相互作用を制御し,cBAF機能とゲノム局所化に影響を与えます.

科学分野:

分子生物学
クロマチン生物学
タンパク質の生化学

背景:

本質的に無秩序な領域 (IDR) は核タンパク質の重要な部分を構成する.
IDRは,進化的制約がないため,伝統的に非特異的な相互作用を媒介すると考えられていた.

研究の目的:

cBAFクロマチンリモデレータのARID1A/BサブユニットのIDR内のシーケンスの特徴的な役割を調査する.
IDR がコンデンサート形成と特定のタンパク質の相互作用に寄与するメカニズムを解明する.

主な方法:

ARID1A/B IDR内の配列組成と分布の分析
配列の変化が凝縮物形成とタンパク質の相互作用に与える影響を評価する.
細胞モデルにおけるcBAFクロマチンの局所化と活性に対するIDR配列の機能的影響を評価する.

主要な成果:

コンデンサートの形成は均等に分布したチロシン残留物によって引き起こされ,特定のパートナー相互作用は,アラニン,グリシン,グルタミンなどの非ランダムなブロックによって媒介されます.
これらの異なる配列のグラマーは,特定のcBAFタンパク質相互作用ネットワークを集約する.
ARID1B IDR配列の文法に影響する病気に関連した変異は,cBAF機能とクロマチンの局所化を損なう.

結論:

IDRには特定のシーケンスの文法があり,フェーズ分離とパートナーの採用を含む異なる機能を指示します.
IDRによって媒介される相分離は,染色体改造においてゲノム局所化と機能的なパートナー採用の両方を達成するためのメカニズムである.
IDR配列の文法を理解することは,染色体リモデラーの機能と疾患メカニズムを理解するために不可欠です.

キーワード:

アリッド1A ARID1B について ATP依存クロマチンの改造 IDR について cBAF複合体コンデンサ本質的に無秩序な地域哺乳類のSWI/SNF複合体段階分離転写因子

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