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DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2.

Msx2 is a mammalian homeodomain protein that is expressed during craniofacial development. A proline-to-histidine substitution at residue 148 of human Msx2 results in an autosomal dominant form of craniosynostosis. In this study, both wild-type and mutant Msx2 were shown to specifically bind to a DNA sequence previously identified as a high-affinity binding site for the related homeodomain protein Msx1. In co-transfection assays both wild-type and mutant Msx2 repressed reporter gene transcription in a dose-dependent but binding-site-independent manner. These results provide evidence that Msx2 is a transcriptional repressor and suggest that the mutant form of Msx2 may exert its pathophysiologic effects on craniofacial development by a gain-of-function mechanism.[1]

References

  1. DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2. Semenza, G.L., Wang, G.L., Kundu, R. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
 
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