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

• Published in: PloS one Vol. 8; no. 1; p. e52689
• Main Authors: Bhatnagar, Anushree, Unal, Hamiyet, Jagannathan, Rajaganapathi, Kaveti, Suma, Duan, Zhong-Hui, Yong, Sandro, Vasanji, Amit, Kinter, Michael, Desnoyer, Russell, Karnik, Sadashiva S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2013; Public Library of Science (PLoS)
• Subjects: Activation; Amino Acid Motifs - genetics; Amino Acid Sequence; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Animals; Biology; Cardiology; Cell Nucleus - genetics; Cell Nucleus - metabolism; Cells, Cultured; Chromatin; Chromatin - genetics; Chromatin - metabolism; Cytomegalovirus; Cytosol; Depletion; Drosophila; Epigenetics; G protein-coupled receptors; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene regulation; Gene Regulatory Networks; Genes; Genomes; GTP-Binding Protein beta Subunits - genetics; GTP-Binding Protein beta Subunits - metabolism; GTP-Binding Protein gamma Subunits - genetics; GTP-Binding Protein gamma Subunits - metabolism; HEK293 Cells; Histones; Histones - genetics; Histones - metabolism; Humans; Immunoblotting; Immunoglobulins; Insects; Laboratories; Localization; Mass spectrometry; MEF2 Transcription Factors; Mice; Mice, Inbred C57BL; Modulators; Molecular Sequence Data; Myocyte enhancer factor 2; Myogenic Regulatory Factors - genetics; Myogenic Regulatory Factors - metabolism; Nuclei; Nucleotide sequence; Protein Binding; Protein interaction; Proteins; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; RNA Interference; Scientific imaging; Sequence Homology, Amino Acid; Transcription factors; Transduction; Cleveland Ohio; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052689

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