Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation

The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that direct...

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Bibliographic Details
Published in:Genes & development 2012-10, Vol.26 (19), p.2192-2205
Main Authors: Yin, Jing-wen, Liang, Yan, Park, Ji Yeon, Chen, Dongrui, Yao, Xiao, Xiao, Qi, Liu, Zhen, Jiang, Bo, Fu, Yu, Bao, Menghan, Huang, Yan, Liu, Yuting, Yan, Jun, Zhu, Min-sheng, Yang, Zhongzhou, Gao, Pingjin, Tian, Bin, Li, Dangsheng, Wang, Gang
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Animals
Cell Differentiation
Cell Line
Cercopithecus aethiops
COS Cells
Cytoskeleton - genetics
Cytoskeleton - metabolism
Gene Expression Regulation, Developmental
HeLa Cells
Humans
Mediator Complex - deficiency
Mediator Complex - genetics
Mediator Complex - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Smooth Muscle - cytology
Research Paper
Zebrafish - embryology
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Summary:The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that directs differentiation into smooth muscle cells (SMCs) or adipocytes. Med23 deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Gene profiling revealed that the presence or absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL targeted cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipogenic genes. Mechanistically, MED23 favors ELK1-SRF binding to SMC gene promoters for repression, whereas the lack of MED23 favors MAL-SRF binding to SMC gene promoters for activation. Remarkably, the effect of MED23 on SMC differentiation can be recapitulated in zebrafish embryogenesis. Collectively, our data demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC and growth/adipogenic gene programs, suggesting its "Ying-Yang" function in directing adipogenesis versus SMC differentiation.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.192666.112