ArticleGenetics2014
High-resolution specificity from DNA sequencing highlights alternative modes of Lac repressor binding.
Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Progress in Aptamer Research and Future Applications.ChemistryOpen · 2025Review
- Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.Cell systems · 2024Article
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- KaScape: a sequencing-based method for global characterization of protein‒DNA binding affinity.Scientific reports · 2023Article
- Quantifying the arms race between LINE-1 and KRAB-zinc finger genes through TECookbook.NAR genomics and bioinformatics · 2023Article
- On the dependent recognition of some long zinc finger proteins.Nucleic acids research · 2023Article
- Prediction of protein-ligand binding affinity from sequencing data with interpretable machine learning.Nature biotechnology · 2022Article
- The Non-continuum Nature of Eukaryotic Transcriptional Regulation.Advances in experimental medicine and biology · 2022Article
- Bayesian Markov models improve the prediction of binding motifs beyond first order.NAR genomics and bioinformatics · 2021Article
- Integrating genome sequence and structural data for statistical learning to predict transcription factor binding sites.Nucleic acids research · 2020Article
- How affinity of the ELT-2 GATA factor binding toDevelopment (Cambridge, England) · 2020Article
- Systematic in vitro profiling of off-target affinity, cleavage and efficiency for CRISPR enzymes.Nucleic acids research · 2020Article
- MODER2: first-order Markov modeling and discovery of monomeric and dimeric binding motifs.Bioinformatics (Oxford, England) · 2020Article
- Transcription factor YcjW controls the emergency HNature communications · 2019Article
- Adaptive Landscapes in the Age of Synthetic Biology.Molecular biology and evolution · 2019Review
- Mapping DNA sequence to transcription factor binding energy in vivo.PLoS computational biology · 2019Article
- Price of disorder in the lac repressor hinge helix.Biopolymers · 2019Article
- Comprehensive, high-resolution binding energy landscapes reveal context dependencies of transcription factor binding.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Lactose repressor hinge domain independently binds DNA.Protein science : a publication of the Protein Society · 2018Article
- Quantitative profiling of BATF family proteins/JUNB/IRF hetero-trimers using Spec-seq.BMC molecular biology · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Knowing the specificity of transcription factors is critical to understanding regulatory networks in cells. The lac repressor-operator system has been studied for many years, but not with high-throughput methods capable of determining specificity comprehensively. Details of its binding interaction and its selection of an asymmetric binding site have been controversial. We employed a new method to accurately determine relative binding affinities to thousands of sequences simultaneously, requiring only sequencing of bound and unbound fractions. An analysis of 2560 different DNA sequence variants, including both base changes and variations in operator length, provides a detailed view of lac repressor sequence specificity. We find that the protein can bind with nearly equal affinities to operators of three different lengths, but the sequence preference changes depending on the length, demonstrating alternative modes of interaction between the protein and DNA. The wild-type operator has an odd length, causing the two monomers to bind in alternative modes, making the asymmetric operator the preferred binding site. We tested two other members of the LacI/GalR protein family and find that neither can bind with high affinity to sites with alternative lengths or shows evidence of alternative binding modes. A further comparison with known and predicted motifs suggests that the lac repressor may be unique in this ability and that this may contribute to its selection.
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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.