ArticleNucleic acids research2011
Using a structural and logics systems approach to infer bHLH-DNA binding specificity determinants.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 92 citations in OpenAlex.
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- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.Cell reports · 2025Article
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- Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable machine learning.Nucleic acids research · 2025Article
- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.bioRxiv : the preprint server for biology · 2025Article
- Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.Nature communications · 2025Article
- Transcription factor 25 modulates gametocytogenesis and ribosome biogenesis in the malaria parasiteFrontiers in cellular and infection microbiology · 2025Article
- Recruitment of homodimeric proneural factors by conserved CAT-CAT E-boxes drives major epigenetic reconfiguration in cortical neurogenesis.Nucleic acids research · 2024Article
- Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency.Journal of clinical immunology · 2024Article
- Transcription factor binding site divergence across maize inbred lines drives transcriptional and phenotypic variation.bioRxiv : the preprint server for biology · 2024Article
- Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation.Nucleic acids research · 2023Article
- Homologous basic helix-loop-helix transcription factors induce distinct deformations of torsionally-stressed DNA: a potential transcription regulation mechanism.QRB discovery · 2022Article
- Multiple neural bHLHs ensure the precision of a neuronal specification event in Caenorhabditis elegans.Biology open · 2021Article
- Mechanisms of Binding Specificity among bHLH Transcription Factors.International journal of molecular sciences · 2021Review
- Transcription factor 4 and its association with psychiatric disorders.Translational psychiatry · 2021Review
- Emerging Roles of Inhibitor of Differentiation-1 in Alzheimer's Disease: Cell Cycle Reentry and Beyond.Cells · 2020Review
- Structural basis for preferential binding of human TCF4 to DNA containing 5-carboxylcytosine.Nucleic acids research · 2019Article
- Inhibitor of DNA binding in heart development and cardiovascular diseases.Cell communication and signaling : CCS · 2019Review
- The Transcriptional Control of Iron Homeostasis in Plants: A Tale of bHLH Transcription Factors?Frontiers in plant science · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Numerous efforts are underway to determine gene regulatory networks that describe physical relationships between transcription factors (TFs) and their target DNA sequences. Members of paralogous TF families typically recognize similar DNA sequences. Knowledge of the molecular determinants of protein-DNA recognition by paralogous TFs is of central importance for understanding how small differences in DNA specificities can dictate target gene selection. Previously, we determined the in vitro DNA binding specificities of 19 Caenorhabditis elegans basic helix-loop-helix (bHLH) dimers using protein binding microarrays. These TFs bind E-box (CANNTG) and E-box-like sequences. Here, we combine these data with logics, bHLH-DNA co-crystal structures and computational modeling to infer which bHLH monomer can interact with which CAN E-box half-site and we identify a critical residue in the protein that dictates this specificity. Validation experiments using mutant bHLH proteins provide support for our inferences. Our study provides insights into the mechanisms of DNA recognition by bHLH dimers as well as a blueprint for system-level studies of the DNA binding determinants of other TF families in different model organisms and humans.
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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.