Résumé :
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Myotonic Dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that provokes functional alteration of CUG-binding proteins. Accordingly, several genes with misregulated alternate splicing of pre-mRNA have been linked to clinical symptoms. In a search for additional molecular mechanisms correlating to functional defects in DM1, we have taken the opportunity of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, we have identified a transcription factor, ZNF37A, the expression of which is strongly downregulated. This defect derives from a loss of RNA stability which is controlled by CUGBP1. Loss of expression of ZNF37A leads to an impaired myogenesis similar to that observed in DM1. In keeping with this functional correlate, loss of ZNF37A protein results in changes in expression of one subunit of the receptor for IL13, a cytokine known to play a role in myoblast recruitment during development and regeneration.
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