基因组 lysine 脱甲基酶 JARID1a 激活 CLOCK-BMAL1 并影响昼夜时钟
Luciano DiTacchio1, Hiep D Le, Christopher Vollmers
1Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|October 1, 2011
概括
基因组脱甲基酶JARID1a通过增加基因组乙化和基因表达来增强昼夜节律. 这种蛋白质在动物的核心分子钟表中发挥着至关重要的,非冗余的作用.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 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:
- 循环节律是由涉及CLOCK和BMAL1.1的转录-翻译反循环调节的.
- 基因组蛋白修饰在调节昼夜基因表达方面发挥着作用.
研究的目的:
- 调查JumonjiC (JmjC) 和ARID域含素脱甲酶1a (JARID1a) 在哺乳动物昼夜振荡器中的作用.
- 确定JARID1a影响昼夜基因转录的机制.
主要方法:
- 同免疫沉用于识别蛋白质复合体.
- 染色体免疫沉以评估促进体的招募和基因素乙化.
- 在哺乳动物细胞中减少JARID1a的RNA干扰.
- 对昼夜基因表达和节律周期的分析.
- 使用Drosophila melanogaster模型研究JARID1a.的同类物.
主要成果:
- JARID1a与CLOCK-BMAL1形成一个复合体,并被招募到Per2促进器中.
- JARID1a以脱甲基酶独立的方式增强了CLOCK-BMAL1介导的转录,部分是通过抑制基因组脱甲基酶1.
- 耗尽JARID1a降低了Per促进体的组分素乙化,抑制了昼夜基因表达,缩短了昼夜周期.
- 德洛索菲拉同类"盖子"的减少表达也改变了昼夜节律.
结论:
- 在哺乳动物的昼夜振荡器中,JARID1a起着非冗余的作用.
- 在昼夜节律中的JARID1a的功能与基因表达的表观遗传调节有关.
- JARID1a的机制涉及与核心时钟机械的相互作用和基因素乙化调节.
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