Interaction of G-protein ?? complex with chromatin modulates GPCR-dependent gene regulation.

ABSTRACT: Heterotrimeric G-protein signal transduction initiated by G-protein-coupled receptors (GPCRs) in the plasma membrane is thought to propagate through protein-protein interactions of subunits, G? and G?? in the cytosol. In this study, we show novel nuclear functions of G?? through demonstrating interaction of G?(2) with integral components of chromatin and effects of G?(2) depletion on global gene expression. Agonist activation of several GPCRs including the angiotensin II type 1 receptor specifically augmented G?(2) levels in the nucleus and G?(2) interacted with specific nucleosome core histones and transcriptional modulators. Depletion of G?(2) repressed the basal and angiotensin II-dependent transcriptional activities of myocyte enhancer factor 2. G?(2) interacted with a sequence motif that was present in several transcription factors, whose genome-wide binding accounted for the G?(2)-dependent regulation of approximately 2% genes. These findings suggest a wide-ranging mechanism by which direct interaction of G?? with specific chromatin bound transcription factors regulates functional gene networks in response to GPCR activation in cells.

SUBMITTER: Bhatnagar A 

PROVIDER: S-EPMC3541368 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature