Analysis of Homeodomain Specificities Allows the Family-wide Prediction of Preferred Recognition Sites
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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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Motifs for DNA-binding proteins can be highly similar among closely related proteins, allowing accurate inference of motifs.
“The motifs for DNA-binding proteins can be highly similar for closely related proteins, allowing accurate inference of motifs7,8”
From A compendium of RNA-binding motifs for decoding gene regulation (2013) · cites this paper as [7]
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- Authors
- Noyes, M. B., Christensen, R. G., Wakabayashi, A., Stormo, G. D., Brodsky, M. H., & Wolfe, S. A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Washington University in St. Louis (US)
- Corresponding author
- Brodsky, Michael H.
- Wolfe, Scot A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 133
- Issue
- 7
- Pages
- 1277-1289
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2478728
- OpenAlex
- W2141354959
- Cited by
- 452
- References
- 54
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 17 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 22 · 2019: 27 · 2018: 26 · 2017: 16 · 2016: 23 · 2015: 27 · 2014: 31 · 2013: 40 · 2012: 35
- FWCI
- 14.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1872 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (HG00249, R21HG003721, R01HG000249, R01HG002673, HG002673)
- National Institute of General Medical Sciences (T32GM08802, T32GM008802)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- homeodomain, DNA binding specificity, homeodomain transcription factor, specificity determinants, Drosophila melanogaster, metazoan genomes
- MeSH terms
- Amino Acid Sequence, Animals, Bacteria, Base Sequence, DNA, Drosophila melanogaster, Humans, Models, Molecular, Phylogeny, Protein Engineering, Protein Structure, Tertiary, Homeodomain Proteins, Two-Hybrid System Techniques, Drosophila Proteins, Genome, Insect
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