Methylation-sensitive DNA binding by v-myb and c-myb proteins

The retroviral oncogene v-myb and its cellular homolog c-myb encode nuclear DNA-binding phosphoproteins (v-MYB and c-MYB) that function as transcriptional regulators. v-MYB and c-MYB recognize a nucleotide sequence motif, PyAACG/TG, that is present in the promoter region of the myb-inducible mim-1 gene and is required for regulation of mim-1 expression by v-MYB and c-MYB. Since the myb-binding motif contains a CpG dinucleotide that constitutes a potential target for methylation, we have investigated whether recognition of the binding site by myb proteins is sensitive to CpG methylation of the binding motif. The results presented here demonstrate that bacterially expressed v-MYB as well as authentic v-MYB and c-MYB bind to the myb binding site in a methylation-sensitive manner. Our observations raise the interesting possibility that myb function can be regulated by methylation of myb binding sites.