1. The Mediator subunit MED20 organizes the early adipogenic complex to promote development of adipose tissues and diet-induced obesity.
- Author
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Tang WS, Weng L, Wang X, Liu CQ, Hu GS, Yin ST, Tao Y, Hong NN, Guo H, Liu W, Wang HR, and Zhao TJ
- Subjects
- Animals, Humans, Mice, 3T3-L1 Cells, Adipocytes metabolism, Alleles, Base Sequence, CCAAT-Enhancer-Binding Protein-beta metabolism, Enhancer Elements, Genetic genetics, HEK293 Cells, Mice, Inbred C57BL, PPAR gamma genetics, PPAR gamma metabolism, Proteins metabolism, Proteolysis, Receptors, Interleukin-17 metabolism, RNA Polymerase II metabolism, Substrate Specificity, Transcription, Genetic, Adipogenesis, Adipose Tissue, Brown metabolism, Diet, Obesity metabolism, Obesity pathology, Protein Subunits metabolism
- Abstract
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/EBPβ and RNA polymerase II to promote transcription of the central adipogenic factor, PPARγ. Our findings have thus uncovered a critical role of MED20 in promoting adipogenesis, development of adipose tissue and diet-induced obesity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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