生物钟负反的分子机制
Hao A Duong1, Maria S Robles, Darko Knutti
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
概括
哺乳动物的昼夜节律依赖于PERIOD蛋白质. 这项研究揭示了与PSF和SIN3A一起的PER复合体如何招募基因组脱乙酶来抑制Per1转录,阐明了一个关键的负反机制.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 哺乳动物的昼夜节律是由一个涉及CLOCK-BMAL1和PERIOD (PER) 蛋白质的分子反循环调节的.
- 在真核生物的昼夜时钟中,负反的精确分子机制在很大程度上是未知的.
研究的目的:
- 阐明哺乳动物昼夜钟中负反背后的分子机制.
- 确定PER复合体的蛋白成分及其在转录抑制中的作用.
主要方法:
- 从小鼠组织中净化和分析PER蛋白复合体.
- 相关蛋白质的识别,包括PSF (聚皮里米丁通道结合蛋白相关拼接因子).
- 研究SIN3A和基因组脱乙酶对Per1促进体的招募.
主要成果:
- 聚乙烯纤维被确定为PER复合物的组成部分.
- 在PER复合体内的PSF招募SIN3A,这是转录抑制复合体的支架.
- 该PER复合物节奏地向Per1促进体递送基因素脱乙酶,抑制Per1的转录.
结论:
- 通过PSF和SIN3A,PER复合体提供了一个生物钟负反的分子机制.
- 这项研究确定了PER复合体在通过表观遗传修饰调节昼夜基因表达中的新功能.
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