NOVEL AP-1 BINDING-SITE CREATED BY DNA-METHYLATION

DNA-methylation is known to repress transcription either by inactivati on of positive regulatory cis-elements containing CpG dinucleotides or via the sequence-nonspecific and methylation-specific binding of inhi biting methyl-CpG binding protein 1 (MeCP1). In the present work we de scribe the novel way DNA-methylation can influence gene expression: a binding site for transcription factors AP-1 might be created by DNA-me thylation. Such a DNA-methylation-dependent AP-1 binding site was foun d in the first intron of the metastasis-associated mts1 gene, The expr ession level of this gene correlates with the hypomethylation of the m ts1 first intron sequence in mouse adenocarcinoma cells. The DNA methy lation-dependent AP-1 binding site was found to be functionally active in the nucleotide context of the mts1 gene. When methylated, this sit e reproducibly repressed transcription of CAT-containing DNA that had been transiently transfected into mouse adenocarcinoma CSML100 cells.