Jhdm2aが代謝性遺伝子発現と肥満に対する耐性を調節する役割
Keisuke Tateishi1, Yuki Okada, Eric M Kallin
1Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Nature
|February 6, 2009
まとめ
ヒストン脱メチラーゼJhdm2aは,代謝遺伝子の調節に不可欠である. マウスの体内でのその欠乏は,脂肪の代謝とエネルギー消費を妨害することで,肥満と高脂血症を引き起こす.
科学分野:
- エピジェネティクス エピジェネティクス
- メタボリズムは
- 分子生物学は分子生物学である.
背景:
- ヒストンのメチル化状態は,酵素によって動的に調節されます.
- Jhdm2a (H3K9特異性デメチラーゼ) は,遺伝子の活性化と男性生殖細胞の発達に関与しています.
研究 の 目的:
- Jhdm2aが代謝性遺伝子発現と体重制御を調節する役割を調査する.
- 代謝調節におけるJhdm2aの機能の基礎となる分子メカニズムを解明する.
主な方法:
- マウスにおけるJhdm2aの遺伝子破壊.
- 肥満と高脂血症を含む代謝パラメータの分析.
- ブラウン脂肪および骨格筋におけるβ-アドレナージ信号伝達経路の調査.
- PparaとUcp1の発現,ヒストンの改変 (H3K9me2) を含む遺伝子調節の分子分析.
主要な成果:
- マウスにおけるJhdm2a機能の喪失は,肥満と高脂血症を引き起こす.
- Jhdm2a欠乏症は,ベータアドレナージック刺激によるグリセロールの放出と茶色脂肪の酸素消費を妨害し,骨格筋の脂肪酸化を低下させます.
- Jhdm2aの発現はベータアドレナジック刺激によって誘発され,PparaとUcp1.1を直接調節する.
- Jhdm2aは,転写因子 (Ppargamma,Rxralpha) とUcp1遺伝子プロモーターの共同活性化剤の徴募を促進する.
結論:
- Jhdm2aは,代謝性遺伝子発現の調節に重要な役割を果たしています.
- Jhdm2aは,マウスの正常な体重管理に不可欠です.
- Jhdm2aは,エネルギー代謝を制御するβ-アドレナージ信号伝達経路の重要な媒介者として作用します.
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