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REV-ERBα influences stability and nuclear localization of the glucocorticoid receptor

ABSTRACT: We report here that REV-ERBα influences nuclear localization of the glucocorticoid receptor and vice versa. As a consequence these two nuclear receptors influence each others transcriptome. REV-ERBα (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 that REV-ERBα 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 as IκB and alcohol dehydrogenase 1 (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.

ORGANISM(S): Mus musculus

PROVIDER: GSE79087 | GEO | 2016/10/01

SECONDARY ACCESSION(S): PRJNA314897

REPOSITORIES: GEO

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Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [ChIP_seq]

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