Gßγ subunits colocalize with RNA polymerase II and regulate transcription in cardiac fibroblasts.
J Biol Chem
; 299(4): 103064, 2023 04.
Article
in En
| MEDLINE
| ID: mdl-36841480
ABSTRACT
Gßγ subunits mediate many different signaling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear Gßγ signaling, we investigated the functional role of Gßγ signaling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. We identified a novel, negative, regulatory role for the Gß1γ dimer in the fibrotic response. Depletion of Gß1 led to derepression of the fibrotic response at the mRNA and protein levels under basal conditions and an enhanced fibrotic response after sustained stimulation of the angiotensin II type I receptor. Our genome-wide chromatin immunoprecipitation experiments revealed that Gß1 colocalized and interacted with RNA polymerase II on fibrotic genes in an angiotensin II-dependent manner. Additionally, blocking transcription with inhibitors of Cdk9 prevented association of Gßγ with transcription complexes. Together, our findings suggest that Gß1γ is a novel transcriptional regulator of the fibrotic response that may act to restrict fibrosis to conditions of sustained fibrotic signaling. Our work expands the role for Gßγ signaling in cardiac fibrosis and may have broad implications for the role of nuclear Gßγ signaling in other cell types.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
RNA Polymerase II
/
Gene Expression Regulation
/
GTP-Binding Protein beta Subunits
/
GTP-Binding Protein gamma Subunits
/
Fibroblasts
/
Myocardium
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
2023
Type:
Article
Affiliation country:
Canada