title: FXR mediates a chromatin looping in the GR promoter thus promoting the resolution of colitis in rodents.
abstract: 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.
authors.affiliation: University of Perugia, Department of Experimental and Clinical Medicine, Via E.dal Pozzo 06126, Perugia, Italy. Electronic address: barbara.renga@unipg.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Amore
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cipriani
authors.forename: Andrea
authors.initials: A
authors.lastname: Mencarelli
authors.forename: Adriana
authors.initials: A
authors.lastname: Carino
authors.forename: Valentina
authors.initials: V
authors.lastname: Sepe
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D014302:Trinitrobenzenesulfonic Acid; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000893:Anti-Inflammatory Agents; D002635:Chenodeoxycholic Acid; D002843:Chromatin; D003907:Dexamethasone; D015735:Mifepristone; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D014302:Trinitrobenzenesulfonic Acid; D000099150:Receptor, Farnesoid X-Activated; C464660:obeticholic acid
keywords: FXR, GR, Chromatin looping, Intestinal immunity, Colitis