RhoA regulation of cardiomyocyte differentiation.
Earlier findings from our laboratory implicated RhoA in heart developmental processes. To investigate factors that potentially regulate RhoA expression, RhoA gene organisation and promoter activity were analysed. Comparative analysis indicated strict conservation of both gene organisation and coding sequence of the chick, mouse, and human RhoA genes. Bioinformatics analysis of the derived promoter region of mouse RhoA identified putative consensus sequence binding sites for several transcription factors involved in heart formation and organogenesis generally. Using luciferase reporter assays, RhoA promoter activity was shown to increase in mouse-derived P19CL6 cells that were induced to differentiate into cardiomyocytes. Overexpression of a dominant negative mutant of mouse RhoA (mRhoAN19) blocked this cardiomyocyte differentiation of P19CL6 cells and led to the accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac α -actin. Taken together, these findings indicate a fundamental role for RhoA in the differentiation of cardiomyocytes.
Department of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0454 Oslo, Norway.
Mari
M
Kaarbø
Denis I
DI
Crane
Wayne G
WG
Murrell
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D020742:rhoA GTP-Binding Protein