Cited by 606Genomics and Chromatin DynamicsProtein Structure and DynamicsDevelopmental Biology and Gene Regulation

Variation in Homeodomain DNA Binding Revealed by High-Resolution Analysis of Sequence Preferences

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Berger, Michael F., Badis, Gwenael, Gehrke, Andrew R., Talukder, Shaheynoor, Philippakis, Anthony A., Peña-Castillo, Lourdes, Alleyne, Trevis M., Mnaimneh, Sanie +9 more·2008·Cell

Abstract

Most homeodomains are unique within a genome, yet many are highly conserved across vast evolutionary distances, implying strong selection on their precise DNA-binding specificities. We determined the binding preferences of the majority (168) of mouse homeodomains to all possible 8-base sequences, revealing rich and complex patterns of sequence specificity and showing that there are at least 65 distinct homeodomain DNA-binding activities. We developed a computational system that successfully predicts binding sites for homeodomain proteins as distant from mouse as Drosophila and C. elegans, and we infer full 8-mer binding profiles for the majority of known animal homeodomains. Our results provide an unprecedented level of resolution in the analysis of this simple domain structure and suggest that variation in sequence recognition may be a factor in its functional diversity and evolutionary success.

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Crossref · 10.1016/j.cell.2008.05.024

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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”

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Authors
Berger, M. F., Badis, G., Gehrke, A. R., Talukder, S., Philippakis, A. A., Peña-Castillo, L., Alleyne, T. M., Mnaimneh, S., Botvinnik, O. B., Chan, E. T., Khalid, F., Zhang, W., Newburger, D., Jaeger, S. A., Morris, Q. D., Bulyk, M. L., & Hughes, T. R.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Toronto (CA)
Corresponding author
  • Bulyk, Martha L.
  • Hughes, Timothy R.
Venue
Cell
Publisher
Elsevier BV
Published
2008-06
Volume
133
Issue
7
Pages
1266-1276
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2080152736
Cited by
606
References
52
Citations by year
2026: 4 · 2025: 19 · 2024: 25 · 2023: 19 · 2022: 22 · 2021: 28 · 2020: 25 · 2019: 28 · 2018: 26 · 2017: 29 · 2016: 36 · 2015: 45 · 2014: 35 · 2013: 57 · 2012: 48
FWCI
21.96
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
Funders
National Human Genome Research Institute (R01HG003985)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
homeodomain, DNA binding specificity, sequence preference, homeodomain transcription factor, binding site prediction, sequence recognition, protein-DNA interactions, evolutionary conservation, Drosophila, Caenorhabditis elegans
MeSH terms
Animals, Base Sequence, DNA, Models, Molecular, Protein Binding, Transcription Factors, Conserved Sequence, Homeodomain Proteins, Evolution, Molecular, Computational Biology, Mice

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