Activation of [beta]-catenin/TCF targets following loss of the tumor suppressor SNF5

The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using co...

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Bibliographic Details
Published inOncogene Vol. 33; no. 7; p. 933
Main Authors Mora-blanco, E L, Mishina, Y, Tillman, E J, Cho, Y-j, Thom, C S, Pomeroy, S L, Shao, W, Roberts, C W M
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group 13.02.2014
Subjects
Cancer
Chromatin
Epigenetics
Gene expression
Mutation
Signal transduction
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Summary:The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies [beta]-catenin hyperactivation and that SNF5 is essential for regulating Wnt/[beta]-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control. [PUBLICATION ABSTRACT]
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2013.37