ヒストンライシンデメチラゼJARID1aは,CLOCK-BMAL1を活性化し,日中時計に影響を与える
Luciano DiTacchio1, Hiep D Le, Christopher Vollmers
1Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
まとめ
ヒストンデメチラゼJARID1aは,ヒストンのアセチル化と遺伝子発現を増加させることで,昼夜リズムを高めます. このタンパク質は,動物のコア分子時計の重要な,非冗長な役割を果たしています.
科学分野:
- 分子生物学は分子生物学である.
- クロノバイオロジー クロノバイオロジー
- エピジェネティクス エピジェネティクス
背景:
- シルカディアンリズムは,CLOCKとBMAL1.1を含むトランスクリプション-トランスレーションフィードバックループによって調節されます.
- ヒストンの改変は,昼間の遺伝子発現を調節する役割を果たします.
研究 の 目的:
- 哺乳類の昼間振動器におけるJumonjiC (JmjC) とARIDドメインを含むヒストンリシン脱メチラーゼ1a (JARID1a) の役割を調査する.
- JARID1aが昼間の遺伝子転写に影響を与えるメカニズムを決定する.
主な方法:
- タンパク質複合体を識別するための共免疫プレシピテーション
- プロモーターの徴募とヒストンのアセチル化を評価するためのクロマチンの免疫プレシピテーション.
- 哺乳類の細胞でJARID1aを枯渇させるRNA干渉.
- 昼間の遺伝子発現とリズム周期の分析.
- Drosophila melanogasterのモデルを利用して,JARID1a.のホモログを研究しました.
主要な成果:
- JARID1aはCLOCK-BMAL1と複合体を形成し,Per2プロモーターに勧誘される.
- JARID1aはCLOCK-BMAL1媒介の転写をデメチラゼから独立して強化し,部分的にはヒストン脱酸化酵素1を阻害する.
- JARID1aの枯渇は,Perプロモーターのヒストンアセチル化を減少させ,昼間の遺伝子発現を抑制し,昼間の期間を短縮します.
- ドロソフィラのホモログ"蓋"の発現が低下すると,昼夜リズムも変化する.
結論:
- JARID1aは,哺乳類の昼間振動器において非冗長な役割を果たしている.
- 昼夜リズムにおけるJARID1aの機能は,遺伝子発現の表遺伝的調節と関連しています.
- JARID1aのメカニズムは,コアクロックメカニズムと相互作用し,ヒストンアセチル化の調節を含む.
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