广泛的负面反应元素通过激素激素结合的葡萄皮质受体直接抑制.
Milan Surjit1, Krishna Priya Ganti, Atish Mukherji
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, Inserm U964, Université de Strasbourg, Collège de France, Illkirch, 67404, France.
Cell
|April 19, 2011
概括
葡萄糖皮质体受体 (GR) 通过结合新型DNA序列 (IR nGREs) 直接抑制基因,独立于以前已知的机制. 这种直接的抑制提供了一种新的基因调节层,通过波动的葡萄皮质激素水平.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
背景情况:
- 葡萄糖皮质体受体 (GR) 通过直接结合到积极的葡萄糖皮质体反应元素 (+GREs) 来调解基因转录.
- 传统上,GR介导的抑制归因于与其他DNA结合因素的间接相互作用.
- 已报告用于压制的直接GR与负GREs (nGREs) 的结合.
研究的目的:
- 研究一种直接GR介导基因抑制的新机制.
- 为了确定参与这种直接抑制的DNA结合序列.
- 为了确定这种调节途径的流行率和生物相关性.
主要方法:
- 在体外和细胞内对GR结合DNA序列的分析.
- 对GR.的新型DNA结合位点 (IR nGREs) 的鉴定.
- 对葡萄糖皮质激素治疗的基因表达反应分析.
- 对基因标的生物信息分析.
主要成果:
- 葡萄糖皮质体受体通过与+GREs无关的简单DNA结合序列 (IR nGREs) 的结合直接抑制转录.
- 这些IR nGREs将抑制器复合体 (SMRT/NCoR) 招募到对抗体结合的GR.
- 超过1000个含有IR nGREs的正基因老鼠和人类基因在体内被葡萄糖皮质类药物抑制.
- 这种机制允许通过不同的葡萄糖皮质激素水平协调基因调节 (激活和抑制).
结论:
- 直接与IR nGREs结合的GR是一种新型的基因抑制机制.
- 这一途径为葡萄皮质皮质体信号传递提供了一个额外的调节层,以响应连接体波动.
- 已识别的IR nGREs存在于大量的基因中,突出显示了这种调节机制的广泛影响.
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