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

Nat Commun. 2019 Oct 10;10(1):4614. doi: 10.1038/s41467-019-12573-z.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Case-Control Studies
  • Colitis / complications
  • Colitis / etiology*
  • Colitis / pathology
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / genetics
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / pathology
  • Mice, Knockout
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Nuclear Proteins
  • Reactive Oxygen Species
  • Transcription Factors
  • SMARCA4 protein, human
  • Smarca4 protein, mouse
  • DNA Helicases