Scanning the human genome with combinatorial transcription factor libraries
- PMID: 12592412
- DOI: 10.1038/nbt794
Scanning the human genome with combinatorial transcription factor libraries
Abstract
Despite the critical importance of transcription factors in mediating gene regulation, there exists no general, genome-wide tool that uses transcription factors to induce or silence a target gene or select for a particular phenotype. In the strategy described here, we prepared large combinatorial libraries of artificial transcription factors comprising three or six zinc-finger domains, and selected transcription factor-DNA interactions able to upregulate several genes in human cells. Selected transcription factors either induced the expression of an endothelial-specific differentiation marker, VE-cadherin, in non-endothelial cell lines or, when combined with a repression domain, knocked down expression. Potential binding sites for a number of these transcription factors were mapped along the promoter of CDH5, the gene encoding VE-cadherin. Transcription factor libraries represent a useful approach for studying and modulating gene function in cells and potentially in whole organisms.
Comment in
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Fingers reach for the genome.Nat Biotechnol. 2003 Mar;21(3):242-3. doi: 10.1038/nbt0303-242. Nat Biotechnol. 2003. PMID: 12610568 No abstract available.
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