雌激素受体调节的转录中的辅因子动态和充分性
1Department of Adult Oncology Dana-Farber Cancer Institute and Harvard Medical School 02115, Boston, MA, USA.
Cell
|January 4, 2001
概括
雌激素受体 (ER) 和联合激活剂以循环模式结合目标基因,驱动基因转录. 这种招募对于雌激素是必不可少的.
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 遗传学 是一个
背景情况:
- 共因子与激素激活的雌激素受体 (ER) 相互作用.
- 经ER介导的基因转录的特定调节者仍然在很大程度上是未知的.
- 目前的模型还不能完全解释激素激活的动态.
研究的目的:
- 为了确定内源性ER介导基因转录的特定调节者.
- 阐明ER和辅助因子对目标基因的动态招募.
- 了解辅激剂在雌激素信号传递和乳腺癌生长中的作用.
主要方法:
- 染色体免疫沉 (ChIP) 用于评估蛋白质-DNA相互作用.
- 使用雌激素和他莫西芬 (TAM) 治疗.
- 采用基因方法来评估协活性剂的功能.
主要成果:
- 在雌激素治疗后,ER和协同激活剂与雌激素反应性促进体呈现出快速,循环的关联.
- 这些招募周期先于转录激活.
- 塔莫西芬 (TAM) 招募核心压缩剂,但不是协同激活剂.
- 招募p160联合激活剂足以激活基因和雌激素的生长效应.
结论:
- 雌激素受体辅助因子的招募以动态的循环模式发生.
- 对于ER介导的基因激活和雌激素在乳腺癌中的增殖作用,p160联合激活剂至关重要.
- 在雌激素信号通路中,ER辅因子起着独特而必不可少的作用.
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