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The chromatin remodelling factor Brg‐1 interacts with β‐catenin to promote target gene activation
Author(s) -
Barker Nick,
Hurlstone Adam,
Musisi Hannah,
Miles Antony,
Bienz Mariann,
Clevers Hans
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.17.4935
Subject(s) - biology , transactivation , chromatin , carcinogenesis , wnt signaling pathway , transcription factor , microbiology and biotechnology , chromatin remodeling , gene expression , regulation of gene expression , gene , beta catenin , promoter , cancer research , genetics
Wnt‐induced formation of nuclear Tcf–β‐catenin complexes promotes transcriptional activation of target genes involved in cell fate decisions. Inappropriate expression of Tcf target genes resulting from mutational activation of this pathway is also implicated in tumorigenesis. The C‐terminus of β‐catenin is indispensable for the transactivation function, which probably reflects the presence of binding sites for essential transcriptional coactivators such as p300/CBP. However, the precise mechanism of transactivation remains unclear. Here we demonstrate an interaction between β‐catenin and Brg‐1, a component of mammalian SWI/SNF and Rsc chromatin‐remodelling complexes. A functional consequence of reintroduction of Brg‐1 into Brg‐1‐deficient cells is enhanced activity of a Tcf‐responsive reporter gene. Consistent with this, stable expression of inactive forms of Brg‐1 in colon carcinoma cell lines specifically inhibits expression of endogenous Tcf target genes. In addition, we observe genetic interactions between the Brg‐1 and β‐catenin homologues in flies. We conclude that β‐catenin recruits Brg‐1 to Tcf target gene promoters, facilitating chromatin remodelling as a prerequisite for transcriptional activation.