title: Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation.
abstract: Oligonucleotides that bind to duplex DNA in a sequence-specific manner by triple helix formation offer an approach to the experimental manipulation of sequence-specific protein binding. Micromolar concentrations of pyrimidine oligodeoxyribonucleotides are shown to block recognition of double helical DNA by prokaryotic modifying enzymes and a eukaryotic transcription factor at a homopurine target site. Inhibition is sequence-specific. Oligonucleotides containing 5-methylcytosine provide substantially more efficient inhibition than oligonucleotides containing cytosine. The results have implications for gene-specific repression by oligonucleotides or their analogs.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125.
authors.forename: L J
authors.initials: LJ
authors.lastname: Maher
authors.forename: B
authors.initials: B
authors.lastname: Wold
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D044503:5-Methylcytosine; D000818:Animals; D001483:Base Sequence; D003596:Cytosine / Q000031:analogs & derivatives; D004247:DNA / Q000378:metabolism*; D004262:DNA Restriction Enzymes; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D008668:Metallothionein; D004262:DNA Restriction Enzymes; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases