Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands.

Abstract:

:Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.

authors

Dickinson LA,Gulizia RJ,Trauger JW,Baird EE,Mosier DE,Gottesfeld JM,Dervan PB

doi

10.1073/pnas.95.22.12890

subject

Has Abstract

pub_date

1998-10-27 00:00:00

pages

12890-5

issue

22

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

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