ArticleGenome research2012
Exploring the DNA-recognition potential of homeodomains.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable machine learning.Nucleic acids research · 2025Article
- Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA.Biochimica et biophysica acta. Gene regulatory mechanisms · 2025Review
- Modelling a pathological GSX2 variant that selectively alters DNA binding reveals hypomorphic mouse brain defects.Disease models & mechanisms · 2025Article
- Cancer-Targeting Applications of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Cooperative Gsx2-DNA binding requires DNA bending and a novel Gsx2 homeodomain interface.Nucleic acids research · 2024Article
- DNA binding analysis of rare variants in homeodomains reveals homeodomain specificity-determining residues.Nature communications · 2024Article
- Pathogenic variants inGenome research · 2024Article
- Transcriptional precision in photoreceptor development and diseases - Lessons from 25 years of CRX research.Frontiers in cellular neuroscience · 2024Review
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- Sharing DNA-binding information across structurally similar proteins enables accurate specificity determination.Nucleic acids research · 2020Article
- Balance between DNA-binding affinity and specificity enables selective recognition of longer target sequences in vivo.Protein science : a publication of the Protein Society · 2019Article
- Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis.Scientific reports · 2018Article
- Homeobox Gene Duplication and Divergence in Arachnids.Molecular biology and evolution · 2018Article
- Identification of a transcriptional activation domain in yeast repressor activator protein 1 (Rap1) using an altered DNA-binding specificity variant.The Journal of biological chemistry · 2017Article
- Homeodomain proteins: an update.Chromosoma · 2016Review
- Multi-reporter selection for the design of active and more specific zinc-finger nucleases for genome editing.Nature communications · 2016Article
- Absence of a simple code: how transcription factors read the genome.Trends in biochemical sciences · 2014Review
- Protein-DNA binding: complexities and multi-protein codes.Nucleic acids research · 2014Review
- Covariation between homeodomain transcription factors and the shape of their DNA binding sites.Nucleic acids research · 2014Article
- Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.Genome research · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The recognition potential of most families of DNA-binding domains (DBDs) remains relatively unexplored. Homeodomains (HDs), like many other families of DBDs, display limited diversity in their preferred recognition sequences. To explore the recognition potential of HDs, we utilized a bacterial selection system to isolate HD variants, from a randomized library, that are compatible with each of the 64 possible 3' triplet sites (i.e., TAANNN). The majority of these selections yielded sets of HDs with overrepresented residues at specific recognition positions, implying the selection of specific binders. The DNA-binding specificity of 151 representative HD variants was subsequently characterized, identifying HDs that preferentially recognize 44 of these target sites. Many of these variants contain novel combinations of specificity determinants that are uncommon or absent in extant HDs. These novel determinants, when grafted into different HD backbones, produce a corresponding alteration in specificity. This information was used to create more explicit HD recognition models, which can inform the prediction of transcriptional regulatory networks for extant HDs or the engineering of HDs with novel DNA-recognition potential. The diversity of recovered HD recognition sequences raises important questions about the fitness barrier that restricts the evolution of alternate recognition modalities in natural systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.