DDB1 binds histone reader BRWD3 to activate the transcriptional cascade in adipogenesis and promote onset of obesity
Xu Wang, Haoyan Wang, Guo-Sheng Hu, Wen-Shuai Tang, Li Weng, Yuzhu Zhang, Huiling Guo, Shanshan Yao, Shen-Ying Liu, Guoliang Zhang, Yan Han, Min Liu, Xiaodong Zhang, Xiang Cen, Haifeng Shen, Nengming Xiao, Changqin Liu, Hongrui Wang, Jing Huang, Wen Liu, Peng Li, Tong‐Jin Zhao
Abstract
mice show delayed postnatal development of white adipose tissues and are protected from diet-induced obesity. Mechanistically, by interacting with BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of ELK1 downstream immediate early response genes and facilitates the release of paused RNA polymerase II, thereby activating the transcriptional cascade in adipogenesis. Our findings have uncovered a CUL4-independent function of DDB1 in promoting the transcriptional cascade of adipogenesis, development of adipose tissues, and onset of obesity.