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研究表明APC/C控制细胞身份
2020-02-29 23:46

美国加州大学伯克利分校Michael Rape研究组探明后期促进复合物(APC/C)控制基因表达和细胞身份。相关论文于2020219日发表在《自然》杂志上。

他们确定了泛素依赖性机制,该机制将基因表达与细胞分裂整合在一起以保留细胞身份。他们发现WDR5TBP,结合活跃的间期启动子,在有丝分裂期间募集APC/C到特定的转录起始位点。这允许APC/C泛素化组蛋白(也称为VCPLys11Lys48K11 / K48分支的泛素链)位点以募集p97和蛋白酶体,并确保多能性基因在下一细胞周期快速表达。

因此,有丝分裂的完成和转录的重新启动由单个调控子(APC /C)控制,该调控子提供了一种在整个细胞分裂过程中维持细胞身份的强大机制。

据了解,后生动物的发展需要祖细胞的强大增殖能力,其身份是由严格控制的转录网络确定的。由于在有丝分裂期间基因表达被整体抑制,因此定义细胞身份的转录程序必须在每个细胞周期中重新启动,但是如何实现这一点却知之甚少。

附:英文原文

Title: Gene expression and cell identity controlled by anaphase-promoting complex

Author: Eugene Oh, Kevin G. Mark, Annamaria Mocciaro, Edmond R. Watson, J. Rajan Prabu, Denny D. Cha, Martin Kampmann, Nathan Gamarra, Coral Y. Zhou, Michael Rape

Issue&Volume: 2020-02-19

Abstract: Metazoan development requires the robust proliferation of progenitor cells, the identities of which are established by tightly controlled transcriptional networks1. As gene expression is globally inhibited during mitosis, the transcriptional programs that define cell identity must be restarted in each cell cycle2,3,4,5 but how this is accomplished is poorly understood. Here we identify a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active interphase promoters6,7, recruit the anaphase-promoting complex (APC/C) to specific transcription start sites during mitosis. This allows APC/C to decorate histones with ubiquitin chains branched at Lys11 and Lys48 (K11/K48-branched ubiquitin chains) that recruit p97 (also known as VCP) and the proteasome, which ensures the rapid expression of pluripotency genes in the next cell cycle. Mitotic exit and the re-initiation of transcription are thus controlled by a single regulator (APC/C), which provides a robust mechanism for maintaining cell identity throughout cell division.

DOI: 10.1038/s41586-020-2034-1

Source: https://www.nature.com/articles/s41586-020-2034-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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