甲状腺激素受体通过相反的转录效应与甲状腺激素和雌激素反应元素中的共同序列动图结合
C K Glass1, J M Holloway, O V Devary
1Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla 92093-0613.
Cell
|July 29, 1988
概括
甲状腺激素 (T3) 受体结合特定的DNA序列,激活转录. 然而,它们在没有激活的情况下与雌激素反应元素结合,抑制雌激素.
科学领域:
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
- 遗传学 是一个遗传学.
背景情况:
- 甲状腺激素 (T3) 受体调节基因表达.
- 雌激素反应元件 (ERE) 是由雌激素受体结合的DNA序列.
- 对于T3受体转录激活的精确DNA结合要求尚未完全理解.
研究的目的:
- 为了研究T3受体的DNA结合特异性.
- 为了确定T3受体与雌激素反应元素结合的功能后果.
- 阐明T3受体与ERE相互作用的机制.
主要方法:
- 电泳运动转移试验 (EMSAs) 来评估体外DNA结合.
- 在体内转录激活测试使用记者基因系统.
- 对DNA序列的分析,其中包括中央帕林德罗姆图案的变化.
主要成果:
- T3受体结合于具有帕林德罗姆核心基因 (5 个奥米诺-TCAGGTCA.TGACCTGA-3 奥米诺) 和中央"差距"的DNA序列.
- 在体外,T3受体与ERE (缺乏间隙) 高 afinity 结合.
- 在体内,T3受体无法激活ERE的转录,并抑制雌激素介导的交换活化.
结论:
- 只有T3受体DNA结合元件的一个子集作为T3反应元件起作用.
- 与ERE结合的T3受体在转录上是不活跃的,并与雌激素受体结合竞争.
- 这种竞争导致雌激素依赖基因表达的净减少.
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