Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands
| Autor: | Joel M. Gottesfeld, Donald E. Mosier, Richard J. Gulizia, John W. Trauger, Eldon E. Baird, Peter B. Dervan, Liliane A. Dickinson |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Multidisciplinary
biology General transcription factor Genes Viral Models Genetic Transcription Genetic Response element DNA Footprinting Promoter RNA polymerase II Biological Sciences Molecular biology TATA Box DNA-Binding Proteins Enhancer Elements Genetic DNA Viral biology.protein HIV-1 Humans Transcription factor II F RNA Polymerase II Transcription factor II D RNA polymerase II holoenzyme Transcription factor II B Caltech Library Services |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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