Novel AP-1 binding site created by DNA-methylation.
DNA-methylation is known to repress transcription either by inactivation of positive regulatory cis-elements containing CpG dinucleotides or via the sequence-nonspecific and methylation-specific binding of inhibiting methyl-CpG dinucleotides or via the sequence-nonspecific and methylation-specific binding of inhibiting methyl-CpG binding protein 1 (MeCP1). In the present work we describe the novel way DNA-methylation can influence gene expression: a binding site for transcription factors AP-1 might be created by DNA-methylation. Such a DNA-methylation-dependent AP-1 binding site was found in the first intron of the metastasis-associated mts1 gene. The expression level of this gene correlates with the hypomethylation of the mts1 first intron sequence in mouse adenocarcinoma cells. The DNA - methylation-dependent AP-1 binding site was found to be functionally active in the nucleotide context of the mts1 gene. When methylated, this site reproducibly repressed transcription of CAT-containing DNA that had been transiently transfected into mouse adenocarcinoma CSML100 cells.
Tulchinsky
E M
EM
Department of Molecular Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Georgiev
G P
GP
Lukanidin
E M
EM
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D007438:Introns; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases