The caenorhabditis elegans t-box factor mls-1 requires groucho co-repressor interaction for uterine muscle specification

T-box proteins are conserved transcription factors that play crucial roles in development of all metazoans; and,in humans,mutations affecting t-box genes are associated with a variety of congenital diseases and cancers. despite the importance of this transcription factor family,very little is known regarding how t-box factors regulate gene expression. the caenorhabditis elegans genome contains 21 t-box genes,and their characterized functions include cell fate specification in a variety of tissues. the c. elegans tbx1 sub-family member mls-1 functions during larval development to specify the fate of non-striated uterine muscles; and,in mls-1 mutants,uterine muscles are transformed to a vulval muscle fate. here we demonstrate that mls-1 function depends on binding to the groucho-family co-repressor unc-37. mls-1 interacts with unc-37 via a conserved eh1 motif,and the mls-1 eh1 motif is necessary for mls-1 to specify uterine muscle fate. moreover,unc-37 loss-of-function produces uterine muscle to vulval muscle fate transformation similar to those observed in mls-1 mutants. based on these results,we conclude that mls-1 specifies uterine muscle fate by repressing target gene expression,and this function depends on interaction with unc-37. moreover,we suggest that mls-1 shares a common mechanism for transcriptional repression with related t-box factors in other animal phyla. © 2011 miller,okkema.