| First Author | Dean JM | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 1 | Pages | 108228 |
| PubMed ID | 33027649 | Mgi Jnum | J:298822 |
| Mgi Id | MGI:6489025 | Doi | 10.1016/j.celrep.2020.108228 |
| Citation | Dean JM, et al. (2020) MED19 Regulates Adipogenesis and Maintenance of White Adipose Tissue Mass by Mediating PPARgamma-Dependent Gene Expression. Cell Rep 33(1):108228 |
| abstractText | The Mediator complex relays regulatory signals from gene-specific transcription factors to the basal transcriptional machinery. However, the role of individual Mediator subunits in different tissues remains unclear. Here, we demonstrate that MED19 is essential for adipogenesis and maintenance of white adipose tissue (WAT) by mediating peroxisome proliferator-activated receptor gamma (PPARgamma) transcriptional activity. MED19 knockdown blocks white adipogenesis, but not brown adipogenesis or C2C12 myoblast differentiation. Adipose-specific MED19 knockout (KO) in mice results in a striking loss of WAT, whitening of brown fat, hepatic steatosis, and insulin resistance. Inducible adipose-specific MED19 KO in adult animals also results in lipodystrophy, demonstrating its requirement for WAT maintenance. Global gene expression analysis reveals induction of genes involved in apoptosis and inflammation and impaired expression of adipose-specific genes, resulting from decreased PPARgamma residency on adipocyte gene promoters and reduced association of PPARgamma with RNA polymerase II. These results identify MED19 as a crucial facilitator of PPARgamma-mediated gene expression in adipose tissue. |
