We report here that REV-ERB influences nuclear localization of the glucocorticoid receptor and vice versa. As a consequence these two nuclear receptors influence each others transcriptome.;	REV-ERB (Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR,Nr3c1) influences similar processes, but is not part of the circadian clock mechanism although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes we studied the interplay between these two nuclear receptors. We found thatREV-ERB competes with GR for binding to HSP90, a chaperone responsible for the activation of substrate proteins to ensure survival of a cell. This competition affected stability and nuclear localization of GR, thereby affecting GR target gene expression such asIBand alcohol dehydrogenase1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence each others transcritpional potential indicating that the transcriptional landscape is strongly dependent on dynamic processes at the protein level. SOURCE: Sara,S,Fonseca Costa (essepf@gmail.com) -  University of Fribourg

Pluto Bioinformatics

GSE79087: REV-ERB influences stability and nuclear localization of the glucocorticoid receptor