| First Author | Lee JE | Year | 2020 |
| Journal | Mol Cell Biol | Volume | 40 |
| Issue | 17 | PubMed ID | 32601106 |
| Mgi Jnum | J:295426 | Mgi Id | MGI:6460503 |
| Doi | 10.1128/MCB.00209-20 | Citation | Lee JE, et al. (2020) MLL3/MLL4-Associated PAGR1 Regulates Adipogenesis by Controlling Induction of C/EBPbeta and C/EBPdelta. Mol Cell Biol 40(17) |
| abstractText | Transcription factors C/EBPbeta and C/EBPdelta are induced within hours after initiation of adipogenesis in culture. They directly promote the expression of master adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha and are required for adipogenesis in vivo However, the mechanism that controls the induction of C/EBPbeta and C/EBPdelta remains elusive. We previously showed that histone methyltransferases MLL3/MLL4 and associated PTIP are required for the induction of PPARgamma and C/EBPalpha 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/EBPbeta and C/EBPdelta in the early phase of adipogenesis. Deletion of Pagr1 in white and brown preadipocytes prevents the induction of C/EBPbeta and C/EBPdelta and leads to severe defects in adipogenesis. Adipogenesis defects in PAGR1-deficient cells can be rescued by the ectopic expression of C/EBPbeta or PPARgamma. Finally, the deletion of Pagr1 in Myf5(+) precursor cells impairs brown adipose tissue and muscle development. Thus, by controlling the induction of C/EBPbeta and C/EBPdelta, PAGR1 plays a critical role in adipogenesis. |
