The homeobox gene Mohawk represses transcription by recruiting the sin3A/HDAC co-repressor complex.
Mohawk is an atypical homeobox gene expressed in embryonic progenitor cells of skeletal muscle, tendon, and cartilage. We demonstrate that Mohawk functions as a transcriptional repressor capable of blocking the myogenic conversion of 10T1/2 fibroblasts. The repressor activity is located in three small, evolutionarily conserved domains (MRD1-3) in the carboxy-terminal half of the protein. Point mutation analysis revealed six residues in MRD1 are sufficient for repressor function. The carboxy-terminal half of Mohawk is able to recruit components of the Sin3A/HDAC co-repressor complex (Sin3A, Hdac1, and Sap18) and a subset of Polymerase II general transcription factors (Tbp, TFIIA1 and TFIIB). Furthermore, Sap18, a protein that bridges the Sin3A/HDAC complex to DNA-bound transcription factors, is co-immunoprecipitated by MRD1. These data predict that Mohawk can repress transcription through recruitment of the Sin3A/HDAC co-repressor complex, and as a result, repress target genes required for the differentiation of cells to the myogenic lineage.
Anderson
Douglas M
DM
School of Life Sciences, Center for Evolutionary Functional Genomics, Arizona State University, Tempe, Arizona 85287-4501, USA.
Beres
Brian J
BJ
Wilson-Rawls
Jeanne
J
Rawls
Alan
A
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
D018398:Homeodomain Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; C510657:mohawk protein, mouse; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex