通过蛋白质甲基转移酶调节转录
1Department of Pathology HMR 301, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Science (New York, N.Y.)
|June 26, 1999
概括
协同激活剂相关的阿金氨基甲基转移酶1 (CARM1) 通过与p160蛋白结合,增强核受体活性,作为二次协同激活剂. 在CARM1中,CARM1被认为是CARM1.
科学领域:
- 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.
- 基因规则 基因规则
背景情况:
- 协同激活剂的p160家族 (SRC-1,GRIP1/TIF2,p/CIP) 对于核激素受体的转录激活至关重要.
- 核受体介导的转录是各种细胞功能和疾病的关键过程.
研究的目的:
- 调查协活性剂相关的阿尔金因甲基转移酶1 (CARM1) 在核激素受体中介转录中的作用.
- 确定CARM1作为协激活剂的作用机制.
主要方法:
- 同表达试验评估CARM1对核受体转录活性的影响.
- 生物化学测试以确定CARM1与p160联合激活剂的结合相互作用.
- 在体外甲基化试验中,使用素H3.
- 针对位点的突变发生,以探测CARM1.1的S-adenosylmethionine结合域的功能.
主要成果:
- 当与GRIP1或SRC-1a共同表达时,CARM1增强了核受体的转录激活,但不是单独的.
- CARM1与p160联合激活剂的碳基终端区域结合,作为二次联合激活剂发挥作用.
- 在实验室中,CARM1对基因素H3表现出甲基转移酶活性.
- 在CARM1的假定S-adenosylmethionine结合域中发生的突变显著损害了其甲基转移酶和联合激活剂活动.
结论:
- 通过与p160协作激活剂结合,CARM1作为二次协作激活剂,从而增强核受体介导的转录.
- CARM1的甲基转移酶活性,可能通过基因素甲基化,与其协活性剂功能有关.
- 辅激剂介导的蛋白质甲基化是一种新的机制,有助于转录调节.
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