MPP7的L27结构域增强了TAZ-YY1在更新肌肉干细胞方面的合作。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-11-04 DOI:10.1038/s44319-024-00305-4

Anwen Shao, Joseph L Kissil, Chen-Ming Fan

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引用次数: 0

摘要

干细胞再生分化细胞，以维持和修复组织和器官。它们还能自我补充，即自我更新，以支持终生的再生能力。在这里，我们研究了骨骼肌干细胞（MuSC）在再生过程中的更新。转录辅助因子TAZ/YAP（通过TEAD转录因子）调控细胞周期和生长，而转录因子YY1则调控MuSC活化的代谢程序。我们的研究表明，MPP7和AMOT与TAZ和YY1共同调控一些带有TEAD和YY1结合位点的常见基因。在这些常见基因中，Carm1能引导MuSC的更新。我们证明，MPP7的L27结构域增强了TAZ和YY1的相互作用以及转录活性，而AMOT则作为中间体将它们连接在一起。此外，MPP7、TAZ和YY1共同占据了Carm1和其他共同下游基因的启动子。我们的研究结果定义了一个由两个祖先转录程序组成的更新程序，其中选定的关键基因受蛋白质-蛋白质相互作用的调控，并取决于启动子的上下文。

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The L27 domain of MPP7 enhances TAZ-YY1 cooperation to renew muscle stem cells.

Stem cells regenerate differentiated cells to maintain and repair tissues and organs. They also replenish themselves, i.e. self-renew, to support a lifetime of regenerative capacity. Here we study the renewal of skeletal muscle stem cell (MuSC) during regeneration. The transcriptional co-factors TAZ/YAP (via the TEAD transcription factors) regulate cell cycle and growth while the transcription factor YY1 regulates metabolic programs for MuSC activation. We show that MPP7 and AMOT join TAZ and YY1 to regulate a selected number of common genes that harbor TEAD and YY1 binding sites. Among these common genes, Carm1 can direct MuSC renewal. We demonstrate that the L27 domain of MPP7 enhances the interaction as well as the transcriptional activity of TAZ and YY1, while AMOT acts as an intermediate to bridge them together. Furthermore, MPP7, TAZ and YY1 co-occupy the promoters of Carm1 and other common downstream genes. Our results define a renewal program comprised of two progenitor transcriptional programs, in which selected key genes are regulated by protein-protein interactions, dependent on promoter context.

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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