%0 Journal Article
%T Smad7:¦Â-catenin complex regulates myogenic gene transcription
%J -
%D 2019
%R https://doi.org/10.1038/s41419-019-1615-0
%X Recent reports indicate that Smad7 promotes skeletal muscle differentiation and growth. We previously documented a non-canonical role of nuclear Smad7 during myogenesis, independent of its role in TGF-¦Â signaling. Here further characterization of the myogenic function of Smad7 revealed ¦Â-catenin as a Smad7 interacting protein. Biochemical analysis identified a Smad7 interaction domain (SID) between aa575 and aa683 of ¦Â-catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and ¦Â-catenin are cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. Depletion of endogenous Smad7 and ¦Â-catenin in muscle cells reduced ckm promoter activity indicating their role during myogenesis. Deletion of the ¦Â-catenin SID substantially reduced the effect of Smad7 on the ckm promoter and exogenous expression of SID abolished ¦Â-catenin function, indicating that SID functions as a trans dominant-negative regulator of ¦Â-catenin activity. ¦Â-catenin interaction with the Mediator kinase complex through its Med12 subunit led us to identify MED13 as an additional Smad7-binding partner. Collectively, these studies document a novel function of a Smad7-MED12/13-¦Â-catenin complex at the ckm locus, indicating a key role of this complex in the program of myogenic gene expression underlying skeletal muscle development and regeneration
%U https://www.nature.com/articles/s41419-019-1615-0