DDB1 prepares brown adipocytes for cold-induced thermogenesis

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 ac...

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Bibliographic Details
Published in:Life metabolism 2022-11, Vol.1 (1), p.39-53
Main Authors: Wang, Xu, Liu, Shen-Ying, Hu, Guo-Sheng, Wang, Hao-Yan, Zhang, Guo-Liang, Cen, Xiang, Xiang, Si-Ting, Liu, Wen, Li, Peng, Ye, Haobin, Zhao, Tong-Jin
Format: Article
Language:English
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Summary: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 °C 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.
ISSN:2755-0230
2755-0230
DOI:10.1093/lifemeta/loac003