加密染色体调解葡萄糖皮质体受体的节奏抑制
Katja A Lamia1, Stephanie J Papp, Ruth T Yu
1Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. klamia@scripps.edu
Nature
|December 16, 2011
概括
密码染色体1和2调节身体的内部时钟和荷尔蒙反应. 这些蛋白质的损失会破坏葡萄糖代谢,并改变压力激素水平,揭示它们在代谢平衡中的作用.
科学领域:
- 时间生物学 时间生物学
- 分子内分泌学分子内分泌学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 哺乳动物的新陈代谢表现出强烈的昼夜节律,核激素受体表现出白天循环.
- 协调核激素受体和生理时钟的精确机制在很大程度上是未知的.
研究的目的:
- 阐明昼夜共同调节器加密染色体和葡萄糖皮质体受体之间的相互作用.
- 了解密码染色体如何影响对葡萄糖皮质类药物的转录反应,并影响代谢平衡.
主要方法:
- 在小鼠胚胎纤维细胞中研究了加密染色体1/2和葡萄糖皮质体受体之间的依赖联体相互作用.
- 用小鼠模型在体内分析了加密色素缺乏对基因表达和葡萄皮质激素信号的影响.
- 检查了加密染色体的基因组关联与烯酸碳素基因酶1促进体.
主要成果:
- 密码染色体缺陷显著降低了基因抑制和增加了德甲诱导的基因表达,表明密码染色体反对葡萄糖皮质体受体激活.
- 缺乏加密染色体的小鼠表现出葡萄糖不耐受性和高水平的皮质,这表明下丘脑-垂体-上腺轴抑制受损,肝脏葡萄皮质激素的交换活化增加.
- 发现加密染色体1/2与烯酸碳素激酶1促进体结合,其甲诱导的转录在缺乏加密染色体的肝脏中升高.
结论:
- 密码染色体1和2提供了昼夜时钟和葡萄糖皮质体受体活性之间的机械联系.
- 这些发现揭示了加密染色体在通过激素电路的调节来调节代谢平衡中的新作用.
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