GSE163281
The Mediator Subunit MED20 Organizes the Early Adipogenic Complex to Promote Development of Adipose Tissues and Diet-Induced Obesity
MED20 is a non-essential subunit of the transcriptional coactivator Mediator complex, but its physiological function remains largely unknown. Here we show that MED20 plays a key role in the development of adipose tissue and diet-induced obesity. Through affinity purification and candidate screening, we demonstrate that MED20 is targeted for degradation by the anti-obesity CRL4-WDTC1 E3 complex. Depleting MED20 in either 3T3-L1 cells or primary preadipocytes inhibits adipogenesis. Mice with MED20 knocked out in preadipocytes show dramatic defect in the development of brown adipose tissue. Furthermore, removing one allele of Med20 in preadipocytes protects mice from diet-induced obesity, and reverses weight gain in Cul4a- or Cul4b-depleted mice. Mechanistically, MED20 plays a key role in organizing the early adipogenic complex by bridging C/EBPß and RNA polymerase II and thereby stimulating the transcription of PPAR?. Our study has thus identified MED20 as a potential target for obesity treatment. Overall design: ChIP-seq performed in this study was designed to understand the molecular mechanisms underlying MED20 in gene transcription regulation.