MLL3/MLL4-Associated PAGR1 Regulates Adipogenesis by Controlling Induction of C/EBP? and C/EBP?.

ABSTRACT: Transcription factors C/EBP? and C/EBP? are induced within hours after initiation of adipogenesis in culture. They directly promote the expression of master adipogenic transcription factors peroxisome proliferator-activated receptor ? (PPAR?) and C/EBP? and are required for adipogenesis in vivo However, the mechanism that controls the induction of C/EBP? and C/EBP? remains elusive. We previously showed that histone methyltransferases MLL3/MLL4 and associated PTIP are required for the induction of PPAR? and C/EBP? during adipogenesis. Here, we show MLL3/MLL4/PTIP-associated protein PAGR1 (also known as PA1) cooperates with phosphorylated CREB and ligand-activated glucocorticoid receptor to directly control the induction of C/EBP? and C/EBP? in the early phase of adipogenesis. Deletion of Pagr1 in white and brown preadipocytes prevents the induction of C/EBP? and C/EBP? and leads to severe defects in adipogenesis. Adipogenesis defects in PAGR1-deficient cells can be rescued by the ectopic expression of C/EBP? or PPAR?. Finally, the deletion of Pagr1 in Myf5+ precursor cells impairs brown adipose tissue and muscle development. Thus, by controlling the induction of C/EBP? and C/EBP?, PAGR1 plays a critical role in adipogenesis.

SUBMITTER: Lee JE 

PROVIDER: S-EPMC7431048 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature