在调节代谢基因表达和抗肥胖的Jhdm2a的作用
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
概括
基因组脱甲基酶Jhdm2a对于调节代谢基因至关重要. 在小鼠中缺少它会导致肥胖和高脂血症,因为它会破坏脂肪代谢和能量消耗.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢过程中的代谢.
- 分子生物学分子生物学
背景情况:
- 基因组甲基化状态由酶动态调节.
- Jhdm2a (H3K9特异性去甲基酶) 参与基因激活和男性生殖细胞的发育.
研究的目的:
- 研究Jhdm2a在调节代谢基因表达和体重控制中的作用.
- 阐明Jhdm2a在代谢调节中的功能背后的分子机制.
主要方法:
- 在小鼠中Jhdm2a的基因破坏.
- 分析代谢参数,包括肥胖和超脂血症.
- 调查棕色脂肪和骨肌肉中的β-上腺素信号通路.
- 对基因调节的分子分析,包括Ppara和Ucp1的表达,以及基因素修饰 (H3K9me2).
主要成果:
- 在小鼠中,Jhdm2a功能的丧失导致肥胖和高脂血症.
- 缺少Jhdm2a会破坏β-上腺刺激的甘油释放和棕色脂肪的氧气消耗,并降低骨肌肉中的脂肪氧化.
- Jhdm2a表达是由β-上腺素刺激诱导的,并直接调节Ppara和Ucp1.
- Jhdm2a促进转录因子 (Ppargamma,Rxralpha) 和对Ucp1基因促进体的联合激活剂的招募.
结论:
- Jhdm2a在调节代谢基因表达方面发挥着重要作用.
- Jhdm2a对于小鼠的正常体重控制至关重要.
- 在控制能量代谢的β-上腺体信号通路中,Jhdm2a起着关键的调解作用.
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