Oligomeric form of C-terminal-binding protein coactivates NeuroD1-mediated transcription.

Oligomeric form of C-terminal-binding protein coactivates NeuroD1-mediated transcription.
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C 端结合蛋白的寡聚形式共激活 NeuroD1 介导的转录。

DOI:
10.1002/1873-3468.12501
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发表时间:
2017
期刊:
影响因子:
3.5
通讯作者:
Leiter,AndrewB
Leiter,AndrewB
中科院分区:
生物学3区
文献类型:
--
作者:
Ray,SubirK;Li,HuiJ;Leiter,AndrewB

文献摘要

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辅阻遏物C末端结合蛋白(CtBP)的转录共激活机制尚未建立。我们之前发现CtBP与转录因子NeuroD1共同占据了几个活跃转录的内分泌基因,通过招募KDM1A和CoREST来矛盾地增加转录。虽然CtBP的寡聚形式的共抑制的重要性是公认的,寡聚化在转录共激活中的作用很少受到关注。在这里,我们通过在内源性CtBP缺失的细胞中表达CtBP二聚化突变体,研究了CtBP寡聚状态对NeuroD1依赖性转录共激活的重要性。二聚化突变体未能增加转录或与KDM1A和CoREST相关,这表明需要寡聚而不是单体CtBP来招募激活转录所需的其他蛋白质。
The mechanism underlying transcriptional coactivation by the corepressor C‐terminal‐binding protein (CtBP) is not established. We previously found that CtBP co‐occupies several actively transcribed endocrine genes with the transcription factor NeuroD1 to paradoxically increase transcription by recruiting KDM1A and CoREST. While the importance of the oligomeric form of CtBP for corepression is well established, the role of oligomerization in transcriptional coactivation has received little attention. Here, we examined the importance of the oligomeric state of CtBP for coactivation of NeuroD1‐dependent transcription by expressing a CtBP dimerization mutant in cells depleted of endogenous CtBP. Dimerization mutants failed to increase transcription or to associate with KDM1A and CoREST, suggesting that oligomeric, but not monomeric CtBP is required to recruit other proteins needed to activate transcription.