Scanning the human genome with combinatorial transcription factor libraries.

Pilar Blancafort, Laurent Magnenat, Carlos Barbas

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)269-74
JournalNature Biotechnology
Volume21
Issue number3
Publication statusPublished - 2003

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