An interaction between Gß? and RNA polymerase II regulates transcription in cardiac fibroblasts

Gß? subunits are involved in an array of different signalling processes in various compartments of the cell, including the nucleus. To gain further insight into the functions of nuclear Gß?, we investigated the functional role of Gß? signalling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Here, we demonstrate that following activation of the angiotensin II type I receptor in these cells, Gß? dimers interact with RNA polymerase II (RNAPII). Our findings suggest that Gß1 recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. The Gß?-RNAPII interaction was also investigated in HEK 293 cells and was regulated by signaling pathways that diverged from those operating in cardiac fibroblasts, suggesting that although it may be a conserved feature of transcriptional regulation, such regulation may be cell-specific. Taken together, our studies reveal a novel interaction between Gß? subunits and RNA polymerase II and expand the role for Gß? signalling in cardiac fibrosis. Overall design: Gß1 and RNAPII ChIP-seq from neonatal rat cardiac fibroblasts