DDB1 prepares brown adipocytes for cold-induced thermogenesis  

作　　者：Xu Wang Shen-Ying Liu Guo-Sheng Hu Hao-Yan Wang Guo-Liang Zhang Xiang Cen Si-Ting Xiang Wen Liu Peng Li Haobin Ye Tong-Jin Zhao 

机构地区：[1]State Key Laboratory of Genetic Engineering,Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Zhongshan Hospital,Fudan University,Shanghai,China [2]Shanghai Qi Zhi Institute,Shanghai,China [3]School of Pharmaceutical Sciences,Fujian Provincial Key Laboratory of Innovative Drug Target Research,Xiamen University,Xiamen,Fujian,China [4]State Key Laboratory of Cellular Stress Biology,School of Life Sciences,Xiamen University,Xiamen,Fujian,China [5]State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China

出　　处：《Life Metabolism》2022年第1期39-53,共15页生命（代谢（英文）

基　　金：This work was supported by the National Key R&D Program of China(2020YFA0803601);the National Natural Science Foundation of China(32125022 and 32101046);the China Postdoctoral Science Foundation(2019M661348 and 2020T130115).

摘　　要：Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding protein 1(DDB1)mediates the rapid transcription of thermogenic genes upon acute cold exposure.Adipose-or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes.These mice develop hypothermia when subjected to acute cold exposure at 4℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation.Mechanistically,DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b(P-TEFb)to release promoter-proximally paused RNA polymerase II(Pol II),thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure.Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.

关 键 词：brown adipose tissue THERMOGENESIS DDB1 RNA polymerase II promoter-proximal pausing UCP1 PGC1α 

分 类 号：R339.6[医药卫生—人体生理学]