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Publication : The Mediator subunit MED20 organizes the early adipogenic complex to promote development of adipose tissues and diet-induced obesity.

First Author  Tang WS Year  2021
Journal  Cell Rep Volume  36
Issue  1 Pages  109314
PubMed ID  34233190 Mgi Jnum  J:321419
Mgi Id  MGI:6874553 Doi  10.1016/j.celrep.2021.109314
Citation  Tang WS, et al. (2021) The Mediator subunit MED20 organizes the early adipogenic complex to promote development of adipose tissues and diet-induced obesity. Cell Rep 36(1):109314
abstractText  MED20 is a non-essential subunit of the transcriptional coactivator Mediator complex, but its physiological function remains largely unknown. Here, we identify MED20 as a substrate of the anti-obesity CRL4-WDTC1 E3 ubiquitin ligase complex through affinity purification and candidate screening. Overexpression of WDTC1 leads to degradation of MED20, whereas depletion of WDTC1 or CUL4A/B causes accumulation of MED20. Depleting MED20 inhibits adipogenesis, and a non-degradable MED20 mutant restores adipogenesis in WDTC1-overexpressing cells. Furthermore, knockout of Med20 in preadipocytes abolishes development of brown adipose tissues. Removing one allele of Med20 in preadipocytes protects mice from diet-induced obesity and reverses weight gain in Cul4a- or Cul4b-depleted mice. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis reveals that MED20 organizes the early adipogenic complex by bridging C/EBPbeta and RNA polymerase II to promote transcription of the central adipogenic factor, PPARgamma. Our findings have thus uncovered a critical role of MED20 in promoting adipogenesis, development of adipose tissue and diet-induced obesity.
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