title: Targeting of the Sp1 binding sites of HIV-1 long terminal repeat with chromomycin. Disruption of nuclear factor.DNA complexes and inhibition of in vitro transcription.
abstract: Sequence selectivity of DNA-binding drugs has recently been reported in a number of studies employing footprinting and gel retardation approaches. In this paper, we studied the biochemical effects of the sequence-selective binding of chromomycin to the long terminal repeat of the human immunodeficiency type I virus. Deoxyribonuclease I (E.C.3.1.21.1) footprinting, arrested polymerase chain reaction, gel retardation and in vitro transcription experiments have demonstrated that chromomycin preferentially interacts with the binding sites of the promoter-specific transcription factor Sp1. Accordingly, interactions between nuclear proteins and Sp1 binding sites are inhibited by chromomycin, and this effect leads to a sharp inhibition of in vitro transcription.
authors.affiliation: Biotechnology Centre, Ferrara University, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Bianchi
authors.forename: M
authors.initials: M
authors.lastname: Passadore
authors.forename: C
authors.initials: C
authors.lastname: Rutigliano
authors.forename: G
authors.initials: G
authors.lastname: Feriotto
authors.forename: C
authors.initials: C
authors.lastname: Mischiati
authors.forename: R
authors.initials: R
authors.lastname: Gambari
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002865:Chromomycins / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D017931:DNA Primers / Q000235:genetics; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002865:Chromomycins; D017931:DNA Primers; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016329:Sp1 Transcription Factor; D004247:DNA