Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation
- Jing-wen Yin1,
- Yan Liang1,
- Ji Yeon Park2,
- Dongrui Chen3,
- Xiao Yao1,
- Qi Xiao4,
- Zhen Liu1,
- Bo Jiang1,7,
- Yu Fu1,
- Menghan Bao1,
- Yan Huang1,
- Yuting Liu5,
- Jun Yan5,
- Min-sheng Zhu4,
- Zhongzhou Yang4,
- Pingjin Gao3,
- Bin Tian2,
- Dangsheng Li6 and
- Gang Wang1,8
- 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 2Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA;
- 3Laboratory of Vascular Biology, Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China;
- 4MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China;
- 5Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 6Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Abstract
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.
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Footnotes
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↵8 Corresponding author
E-mail gwang22{at}sibs.ac.cn
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.192666.112.
- Received March 26, 2012.
- Accepted August 13, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press