通过信号依赖的转录延长来控制可诱导的基因表达
Diana C Hargreaves1, Tiffany Horng, Ruslan Medzhitov
1Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cell
|July 15, 2009
概括
主要响应基因 (PRG) 具有预组装的转录机制,用于快速基因表达. 它们的诱导依赖于信号依赖的延长和mRNA处理,由Brd4-介导的P-TEFb招募促进.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 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:
- 诱导性转录程序涉及具有明显表达动态的初级和二级响应基因 (PRG和SRG).
- PRG和SRG在基因激活期间对蛋白质合成和染色质重塑的要求上有所不同.
研究的目的:
- 与SRG相比,研究PRG的基础状态特征.
- 阐明控制PRG快速诱导的监管机制.
- 为了确定参与PRG激活的关键蛋白质和修改.
主要方法:
- 对预组装的RNA聚合酶II (Pol II) 和基底状态的PRG促进体中的基因组修饰的分析.
- 在PRG诱导过程中对转录延长和mRNA处理的研究.
- 检查P-TEFb和Brd4在PRG激活中的作用.
- 在PRG促进体中检测 histone 乙化 (H4K5/8/12Ac).
主要成果:
- 许多PRG,与SRG不同,基本上表现出预组装的Pol II和积极的基因组修饰在它们的促进体上.
- 在PRG的基底Pol II产生未连接的转录,但在没有刺激的情况下不会产生成熟的mRNA.
- PRG诱导由信号依赖的转录延长和通过P-TEFb招募的mRNA处理来调节.
- Brd4通过在PRG发起者那里识别诱导获得的H4K5/8/12Ac来招募P-TEFb.
结论:
- PRG的允许结构促进了它们独特的基底状态调节,通过核心压力复合体.
- 这种结构还使PRG在各种细胞类型中快速诱导.
- Brd4介导的P-TEFb的招募对于PRG的快速激活至关重要.
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