Structure-based design of transcription factors

Joel L. Pomerantz, Phillip A. Sharp, Carl O. Pabo

Research output: Contribution to journalArticlepeer-review

Abstract

Computer modeling suggested that transcription factors with novel sequence specificities could be designed by combining known DNA binding domains. This structure-based strategy was tested by construction of a fusion protein, ZFHD1, that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and the homeodomain from Oct-1. The fusion protein bound optimally to a sequence containing adjacent homeodomain (TAATTA) and zinc finger (NGGGNG) subsites. When fused to an activation domain, ZFHD1 regulated promoter activity in vivo in a sequence-specific manner. Analysis of known protein-DNA complexes suggests that many other DNA binding proteins could be designed in a similar fashion.

Original languageEnglish (US)
Pages (from-to)93-96
Number of pages4
JournalScience
Volume267
Issue number5194
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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