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

AUTOR(ES)

Dickinson, Liliane A.

FONTE

The National Academy of Sciences

RESUMO

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.

Documentos Relacionados

• Elongation factor SII-dependent transcription by RNA polymerase II through a sequence-specific DNA-binding protein.
• Cryptic DNA-binding domain in the C terminus of RNA polymerase II general transcription factor RAP30.
• Selective inhibition of c-Myb DNA-binding by RNA polymers
• A DNA-binding protein is required for termination of transcription by RNA polymerase I in Xenopus laevis.
• Phage N4 RNA polymerase II recruitment to DNA by a single-stranded DNA-binding protein