TARGETING OF THE SP1 BINDING-SITES OF HIV-1 LONG TERMINAL REPEAT WITHCHROMOMYCIN - DISRUPTION OF NUCLEAR FACTOR-CENTER-DOT-DNA COMPLEXES AND INHIBITION OF IN-VITRO TRANSCRIPTION

Sequence selectivity of DNA-binding drugs has recently been reported i n a number of studies employing footprinting and gel retardation appro aches. In this paper, we studied the biochemical effects of the sequen ce-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 a nd in vitro transcription experiments have demonstrated that chromomyc in preferentially interacts with the binding sites of the promoter-spe cific transcription factor Spl. Accordingly, interactions between nucl ear proteins and Spl binding sites are inhibited by chromomycin, and t his effect leads to a sharp inhibition of in vitro transcription. Copy right (C) 1996 Elsevier Science Inc.