BRG1 attenuates colonic inflammation and tumorigenesis through autophagy-dependent oxidative stress sequestration

Min Liu, Tongyu Sun, Ni Li, Junjie Peng, Da Fu, Wei Li, Li Li () and Wei-Qiang Gao ()
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Min Liu: Shanghai Jiao Tong University
Tongyu Sun: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Ni Li: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Junjie Peng: Fudan University Shanghai Cancer Center
Da Fu: Tongji University School of Medicine
Wei Li: Institute of Zoology, Chinese Academy of Sciences
Li Li: Shanghai Jiao Tong University
Wei-Qiang Gao: Shanghai Jiao Tong University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Autophagy is a central component of integrated stress responses that influences many inflammatory diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the core machinery is known, the molecular basis of the epigenetic regulation of autophagy and its role in colon inflammation remain largely undefined. Here, we report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for the homeostatic maintenance of intestinal epithelial cells (IECs) to prevent the inflammation and tumorigenesis. BRG1 emerges as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Defective autophagy in BRG1-deficient IECs results in excess reactive oxygen species (ROS), which leads to the defects in barrier integrity. Together, our results establish that BRG1 may represent an autophagy checkpoint that is pathogenetically linked to colitis and is therefore likely a potential therapeutic target for disease intervention.

Date: 2019
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DOI: 10.1038/s41467-019-12573-z

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