Glucocorticoid receptor-mediated chromatin circadian misalignment in stress-induced irritable bowel syndrome.

Stress-elevated glucocorticoids cause circadian disturbances and gut-brain axis (GBA) disorders, including irritable bowel syndrome (IBS). We hypothesized that the glucocorticoid receptor (GR/NR3C1) might cause chromatin circadian misalignment in the colon epithelium. We observed significantly decreased core circadian gene in water avoidance stressed (WAS) BALB/c colon epithelium, like in IBS patients. WAS decreased GR binding at the promoter E-box (enhancer box), and GR could suppress via this site. Stress also altered GR binding at the E-box sites along the - chromatin and remodeled circadian chromatin 3D structures, including - super-enhancer, , and . Intestinal deletion of specifically abolished these stress-induced transcriptional alternations relevant to IBS phenotypes in BALB/c mice. GR mediated - chromatin disease related circadian misalignment in stress-induced IBS animal model. This animal model dataset suggests that regulatory SNPs of human - transcription through conserved chromatin looping have translational potential based on the GR-mediated circadian-stress crosstalk.