高濃度BEND3は,分化中に二価遺伝子の早期活性化を防ぐ
Jing Zhang1, Yan Zhang1, Qinglong You1,2
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Science (New York, N.Y.)
|February 10, 2022
まとめ
BEND3はCpGの島結合タンパク質で 胚の発達に不可欠です ポリコンブ抑制複合体2を安定させ,適切な分化を確保することで,二価遺伝子の早期活性化を防ぐ.
科学分野:
- エピジェネティクスと発達生物学
- 分子生物学と細胞生物学
背景:
- 活性および抑制性ヒストンの修正によって特徴づけられる双対遺伝子は,発達活性化に備わっている.
- CpG島 (CGI) メチル化は,発達中の遺伝子発現を調節する上で重要な役割を果たします.
- 遺伝子発現と発達の調節におけるBEND3タンパク質の機能はほとんど不明である.
研究 の 目的:
- 胚の発達と遺伝子調節における BEND3 の役割を調査する.
- BEND3 がDNAに結合し,遺伝子発現に影響を与える分子メカニズムを解明する.
- ポリコンブ抑制複合体2 (PRC2) とのBEND3の相互作用を理解する.
主な方法:
- BEND3を標的DNAで同結晶化して構造を決定する.
- BEND3除去されたマウス胚と胚性幹細胞 (ESC) の生成と分析.
- 双価遺伝子のBEND3とPRC2の占有率を評価するクロマチンの免疫プレシピテーション (ChIP) アッセイ.
主要な成果:
- BEND3はDNAメチル化に敏感なタンパク質で,規制要素のCpG島に結合する.
- BEND3の喪失は,胎盤前期に胚の死亡を引き起こします.
- Bend3 null ESCは,多数の二価遺伝子の早期活性化による重度の差別化欠陥を示します.
- BEND3は,H3K27me3レベルを維持し,PRC2をBEND3を占有する二価遺伝子に安定的に勧誘するために不可欠です.
結論:
- BEND3は重要な表遺伝子調節体として機能し,ESCにおける二価遺伝子の静止状態を維持する.
- BEND3の機能は発達初期に異常遺伝子の活性化を防ぐために不可欠です.
- BEND3の構造と機能の洞察は,発達の進行を保障する役割を強調しています.
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