Structure-Based Design of Transcription Factors
- 6 January 1995
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 267 (5194), 93-96
- https://doi.org/10.1126/science.7809612
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.Keywords
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