title: Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation.
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.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jing-wen
authors.initials: JW
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Dongrui
authors.initials: D
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Yao
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Menghan
authors.initials: M
authors.lastname: Bao
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Min-sheng
authors.initials: MS
authors.lastname: Zhu
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Yang
authors.forename: Pingjin
authors.initials: P
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D015027:Zebrafish / Q000196:embryology
chemical_list: C541034:Med23 protein, mouse; D056892:Mediator Complex