低氧反应的转录延长控制
Shimaa Hassan AbdelAziz Soliman1, Marta Iwanaszko1, Bin Zheng1
1Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
概括
具有BRD4的CDK9复合体,而不是AFF1/4,对于在低氧应激期间释放暂停RNA聚合酶II (RNAPII) 是至关重要的. 这就是BRD4D.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 细胞应激反应的应激反应
背景情况:
- 通过RNA聚合酶II (RNAPII) 进行转录调节,涉及从促进物-近位暂停中控制释放.
- 已知含有CDK9的PTEF-b延长因子可促进RNAPII释放.
- 不同PTEF-b/CDK9复合体在应激反应中的具体作用尚不清楚.
研究的目的:
- 为了识别和描述涉及到对缺氧的转录反应的特定CDK9复合体.
- 阐明BRD4及其基因 (BET) 在缺氧诱导的基因表达中的作用.
- 研究BRD4在低氧压力期间促进RNAPII释放的机制.
主要方法:
- 鉴定和表征CDK9复合体.
- 对低氧反应中BRD4和AFF1/4的参与进行分析.
- 使用JQ1.1.进行BET抑制的评估.
- 研究BRD4的C端区域功能.
- 使用小分子抑制剂破坏聚合酶相关因子-1复合体 (PAF1C).
主要成果:
- 含有BRD4,但不含AFF1/4的CDK9复合体对于低氧应激反应至关重要.
- 在低氧激活基因中,不需要BRD4基因 (BET) 来释放暂停的RNAPII.
- 由JQ1抑制BET不会影响低氧基因反应.
- BRD4的C终端区域对于招募PAF1C来促进低氧反应基因的延伸竞争性RNAPII复合体是必要的.
- 在缺氧期间,PAF1C的破坏会损害BRD4介导的RNAPII释放.
结论:
- 该研究确定了一种特定的BRD4-含有CDK9复合体,该复合体对于转录对缺氧的反应至关重要.
- 通过PAF1C的招募,BRD4的C终端区域在缺氧诱导的RNAPII释放中发挥着关键作用.
- 这些发现提供了对控制低氧反应性转录延长的向机制的见解.
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