title: DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2.
abstract: 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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Semenza
authors.forename: G L
authors.initials: GL
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Kundu
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D009838:Oligodeoxyribonucleotides; D004247:DNA