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PMID: 18585360 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites.

Cell ·Vol. 133 ·No. 7 ·2008-06-27 ·Pages 1277-89

Noyes MB, Christensen RG, Wakabayashi A, Stormo GD, Brodsky MH, Wolfe SA

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Bacteria/chemistry,genetics Base Sequence DNA/chemistry,metabolism Drosophila Proteins/chemistry,genetics Drosophila melanogaster/chemistry,genetics Genome, Insect Homeodomain Proteins/chemistry,genetics Humans Models, Molecular Phylogeny Protein Engineering Protein Structure, Tertiary Two-Hybrid System Techniques
Chemicals
Drosophila Proteins Homeodomain Proteins DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Noyes Marcus B
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Christensen Ryan G
Wakabayashi Atsuya
Stormo Gary D
Brodsky Michael H
Wolfe Scot A
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.05.023
Published
2008-06-27
Pages
1277-89
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2478728
Subset
IM
Grants
NHGRI NIH HHS · R21 HG003721-02 · United States
NHGRI NIH HHS · R21 HG003721 · United States
NHGRI NIH HHS · HG002673 · United States
NIGMS NIH HHS · T32 GM008802 · United States
NHGRI NIH HHS · R01 HG000249 · United States
NHGRI NIH HHS · HG00249 · United States
NHGRI NIH HHS · 1R21HG003721 · United States
NIGMS NIH HHS · T32GM08802 · United States
NHGRI NIH HHS · R01 HG000249-19 · United States
NHGRI NIH HHS · R01 HG002673 · United States
Corrections
CommentIn
PMID: 18585344
External Links
PubMed source DOI: 10.1016/j.cell.2008.05.023 PMC Full Text View journal details
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