脂肪生成
调解人
染色质免疫沉淀
脂肪组织
细胞生物学
辅活化剂
泛素连接酶
生物
蛋白质亚单位
内分泌学
内科学
基因剔除小鼠
泛素
转录因子
生物化学
基因
发起人
医学
基因表达
作者
Wei Tang,Li Weng,Xu Wang,Changqin Liu,Guo-Sheng Hu,Shuting Yin,Tao Ying,Ni-Na Hong,Min Zhang,Wen Li,Hongrui Wang,Tong‐Jin Zhao
出处
期刊:Cell Reports
[Elsevier]
日期:2021-07-01
卷期号:36 (1): 109314-109314
被引量:9
标识
DOI:10.1016/j.celrep.2021.109314
摘要
Summary
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.
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