Journal
CELL
Volume 133, Issue 7, Pages 1277-1289Publisher
CELL PRESS
DOI: 10.1016/j.cell.2008.05.023
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Funding
- NHGRI NIH HHS [R21 HG003721, R21 HG003721-02, HG002673, HG00249, 1R21HG003721, R01 HG000249, R01 HG002673, R01 HG000249-19] Funding Source: Medline
- NIGMS NIH HHS [T32GM08802, T32 GM008802] Funding Source: Medline
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We describe the comprehensive characterization of homeodomain DNA-binding specificities from a metazoan genome. The analysis of all 84 independent homeodomains from D. melanogaster reveals the breadth of DNA sequences that can be specified by this recognition motif. The majority of these factors can be organized into 11 different specificity groups, where the preferred recognition sequence between these groups can differ at up to four of the six core recognition positions. Analysis of the recognition motifs within these groups led to a catalog of common specificity determinants that may cooperate or compete to define the binding site preference. With these recognition principles, a homeodomain can be reengineered to create factors where its specificity is altered at the majority of recognition positions. This resource also allows prediction of homeodomain specificities from other organisms, which is demonstrated by the prediction and analysis of human homeodomain specificities.
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