Journal
CELL REPORTS
Volume 35, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109281
Keywords
-
Categories
Funding
- National Key R&D Program of China [2016YFA0502003, 2020YFA0803600]
- National Natural Science Foundation of China [91857107, 31671223, 31871193, 81772818, 81870611]
- Fundamental Research Funds for the Central Universities [20720180046]
- China Postdoctoral Science Foundation [2019M661348, 2020T130115]
- Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University [SKLCSB2019KF004]
- Project 111'' - State Bureau of Foreign Experts
- Ministry of Education of China [BP2018017]
Ask authors/readers for more resources
The study shows that DDB1 binding to BRWD3 promotes adipogenesis and diet-induced obesity; DDB1 can stimulate adipogenesis independently of CUL4; Ddb1(+/-) mice exhibit delayed postnatal development of white adipose tissues and are protected from diet-induced obesity.
Obesity has become a global pandemic. Identification of key factors in adipogenesis helps to tackle obesity and related metabolic diseases. Here, we show that DDB1 binds the histone reader BRWD3 to promote adipogenesis and diet-induced obesity. Although typically recognized as a component of the CUL4-RING E3 ubiquitin ligase complex, DDB1 stimulates adipogenesis independently of CUL4. A DDB1 mutant that does not bind CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient cells. Ddb1(+/-) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available