α-Catenin is an inhibitor of transcription

alpha-Catenin (alpha-cat) is an actin-binding protein required for cell-cell cohesion. Although this adhesive function for alpha-cat is well appreciated, cells contain a substantial amount of nonjunctional alpha-cat that may be used for other functions. We show that alpha-cat is a nuclear protein that can interact with beta-catenin (beta-cat) and T-cell factor (TCF) and that the nuclear accumulation of alpha-cat depends on beta-cat. Using overexpression, knockdown, and chromatin immunoprecipitation approaches, we show that alpha-cat attenuates Wnt/beta-cat-responsive genes in a manner that is downstream of beta-cat/TCF loading on promoters. Both beta-cat- and actin-binding domains of alpha-cat are required to inhibit Wnt signaling. A nuclear-targeted form of alpha-cat induces the formation of nuclear filamentous actin, whereas cells lacking alpha-cat show altered nuclear actin properties. Formation of nuclear actin filaments correlates with reduced RNA synthesis and altered chromatin organization. Conversely, nuclear extracts made from cells lacking alpha-cat show enhanced general transcription in vitro, an activity that can be partially rescued by restoring the C-terminal actin-binding region of alpha-cat. These data demonstrate that alpha-cat may limit gene expression by affecting nuclear actin organization.