Transcriptional regulation of SM22alpha by Wnt3a: convergence with TGFbeta(1)/Smad signaling at a novel regulatory element.

ABSTRACT: The role of canonical Wnt signaling in myofibroblast biology has not been fully investigated. The C3H10T1/2 mesenchymal cell line recapitulates myofibroblast differentiation in vitro and in vivo, including SM22alpha expression. Using this model, we find that Wnt3a upregulates SM22alpha in concert with TGFbeta(1). Wnt1, Wnt5a and BMP2 could not replace Wnt3a and TGFbeta(1) signals. Chromatin immunoprecipitation identified that Wnt3a enhances both genomic SM22alpha histone H3 acetylation and beta-catenin association, hallmarks of transcriptional activation. By analyzing a series of SM22alpha promoter-luciferase (LUC) reporter constructs, we mapped Wnt3a-regulated DNA transcriptional activation to nucleotides -213 to -192 relative to the transcription initiation site. In gel shift assays, DNA

SUBMITTER: Shafer SL 

PROVIDER: S-EPMC2666882 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature