对于CtBP转录核心压缩器的非结构化C终端域的调节作用
Ana-Maria Raicu1, Megha Suresh2, David N Arnosti2
1Cell and Molecular Biology Program, Michigan State University, East Lansing, MI.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
在C-终端结合蛋白 (CtBP) C-终端域 (CTD) 调节转录抑制. 短CtBP异型 (CtBP(S)) 在体内比长CtBP(L)) 异型更有效地抑制基因.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 发展生物学 发展生物学
背景情况:
- 末结合蛋白 (C-terminal Binding Protein,CtBP) 是一种保存的转录核心压缩剂,对发育和瘤发生至关重要.
- 尽管CtBP在进化过程中得到了保护,但其内在的C终端域 (CTD) 功能不明.
研究的目的:
- 研究CtBP CTD在转录调节中的功能意义.
- 为了比较Drosophila CtBP异型体与CTD和没有CTD的活性.
- 为了确定CTD是否调节CTBP的抑制活动,在体内和体外.
主要方法:
- 利用CRISPRi系统将dCas9-CtBP(L) 和dCas9-CtBP(S) 招募到内源性促进体中.
- 在体内评估Mpp6促进体的转录抑制.
- 在细胞培养中对转染的Mpp6记者基因的异形活性进行比较.
主要成果:
- 在体内,CtBP(S显著抑制了Mpp6促进体转录,而CtBP(L表现出较弱的抑制.
- 在细胞培养中,这两种异型在转染的Mpp6记者上表现出类似的活性.
- 发育调节的异型体在镇压活动中表现出特定环境的差异.
结论:
- CtBP的C端域 (CTD) 以特定的环境方式调节其转录抑制活动.
- CTD可以微调CTBP的镇压能力,以适应特定的发展计划.
- 经发育调节的CtBP异型提供了一系列的抑制活动.
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