FXR mediates a chromatin looping in the GR promoter thus promoting the resolution of colitis in rodents

Glucocorticoids (GCs) are important endocrine regulators of a wide range of physiological processes ranging from immune function to glucose and lipid metabolism. For decades, synthetic glucocorticoids such as dexamethasone have been the cornerstone for the clinical treatment of inflammatory bowel diseases (IBD). A previous study has shown that farnesoid X receptor (FXR) enhances the transcription of NR3C1 gene, which encodes for human GR, by binding to a conserved FXR response element (FXRE) in the distal promoter of this gene. In the present study we demonstrate that FXR promotes the resolution of colitis in rodents by enhancing Gr gene transcription. We used the chromatin conformation capture (3C) assay to demonstrate that this FXRE is functional in mediating a head-to-tail chromatin looping, thus increasing Gr transcription efficiency. These findings underscore the importance of FXR/GR axis in the control of intestinal inflammation.

Graphical abstractThe distal promoter of NR3C1 gene contains an FXRE that facilitates the formation of a head-to-tail chromatin loop, increases GR gene transcription efficiency and is essential to mediate the anti-inflammatory effects of FXR in the intestine.Figure optionsDownload full-size imageDownload high-quality image (90 K)Download as PowerPoint slide