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The homeobox gene Mohawk represses transcription by recruiting the sin3A/HDAC co‐repressor complex
Author(s) -
Anderson Douglas M.,
Beres Brian J.,
WilsonRawls Jeanne,
Rawls Alan
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21873
Subject(s) - repressor , biology , transcription (linguistics) , homeobox , transcription factor , yy1 , microbiology and biotechnology , hdac1 , gene , genetics , promoter , histone , histone deacetylase , gene expression , linguistics , philosophy
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. Developmental Dynamics 238:572–580, 2009. © 2009 Wiley‐Liss, Inc.