title: The Caenorhabditis elegans T-box factor MLS-1 requires Groucho co-repressor interaction for uterine muscle specification.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Miller
authors.forename: Peter G
authors.initials: PG
authors.lastname: Okkema
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057850:Hermaphroditic Organisms; D009154:Mutation; D009215:Myometrium / Q000254:growth & development* / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020825:T-Box Domain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C447844:mls-1 protein, C elegans; C106184:unc-37 protein, C elegans