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 language | English (US) |
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Pages (from-to) | 93-96 |
Number of pages | 4 |
Journal | Science |
Volume | 267 |
Issue number | 5194 |
DOIs | |
State | Published - 1995 |
Externally published | Yes |
ASJC Scopus subject areas
- General