The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation

Wnt-induced formation of nuclear Tcf-beta -catenin complexes promotes trans criptional activation of target genes involved in cell fate decisions. Inap propriate expression of Tcf target genes resulting from mutational activati on of this pathway is also implicated in tumorigenesis. The C-terminus of b eta -catenin is indispensable for the transactivation function, which proba bly reflects the presence of binding sites for essential transcriptional co activators such as p300/CBP. However, the precise mechanism of transactivat ion remains unclear. Here we demonstrate an interaction between beta -caten in and Brg-1, a component of mammalian SWI/SNF and Rsc chromatin-remodellin g complexes. A functional consequence of reintroduction of Brg-1 into Brg-1 -deficient cells is enhanced activity of a Tcf-responsive reporter gene. Co nsistent with this, stable expression of inactive forms of Brg-1 in colon c arcinoma cell lines specifically inhibits expression of endogenous Tcf targ et genes. In addition, we observe genetic interactions between the Brg-1 an d beta -catenin homologues in flies. We conclude that beta -catenin recruit s Brg-1 to Tcf target gene promoters, facilitating chromatin remodelling as a prerequisite for transcriptional activation.