| First Author | Anderson DM | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 42 | Pages | 35351-9 |
| PubMed ID | 22923612 | Mgi Jnum | J:211235 |
| Mgi Id | MGI:5574289 | Doi | 10.1074/jbc.M112.399386 |
| Citation | Anderson DM, et al. (2012) Characterization of the DNA-binding properties of the Mohawk homeobox transcription factor. J Biol Chem 287(42):35351-9 |
| abstractText | The homeobox transcription factor Mohawk (Mkx) is a potent transcriptional repressor expressed in the embryonic precursors of skeletal muscle, cartilage, and bone. MKX has recently been shown to be a critical regulator of musculoskeletal tissue differentiation and gene expression; however, the genetic pathways through which MKX functions and its DNA-binding properties are currently unknown. Using a modified bacterial one-hybrid site selection assay, we determined the core DNA-recognition motif of the mouse monomeric Mkx homeodomain to be A-C-A. Using cell-based assays, we have identified a minimal Mkx-responsive element (MRE) located within the Mkx promoter, which is composed of a highly conserved inverted repeat of the core Mkx recognition motif. Using the minimal MRE sequence, we have further identified conserved MREs within the locus of Sox6, a transcription factor that represses slow fiber gene expression during skeletal muscle differentiation. Real-time PCR and immunostaining of in vitro differentiated muscle satellite cells isolated from Mkx-null mice revealed an increase in the expression of Sox6 and down-regulation of slow fiber structural genes. Together, these data identify the unique DNA-recognition properties of MKX and reveal a novel role for Mkx in promoting slow fiber type specification during skeletal muscle differentiation. |
