ArticleProceedings of the National Academy of Sciences of the United States of America2009
Experimental determination of the evolvability of a transcription factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed.
- Article
- Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.Nature communications · 2025Article
- Cell-Free Gene Expression: Methods and Applications.Chemical reviews · 2025Review
- Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency.Journal of clinical immunology · 2024Article
- Systematic analysis of low-affinity transcription factor binding site clusters in vitro and in vivo establishes their functional relevance.Nature communications · 2022Article
- Bottom-Up Construction of Complex Biomolecular Systems With Cell-Free Synthetic Biology.Frontiers in bioengineering and biotechnology · 2020Review
- Recent insights into the genotype-phenotype relationship from massively parallel genetic assays.Evolutionary applications · 2019Review
- Cell-free gene-regulatory network engineering with synthetic transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The Recruitment Model of Metabolic Evolution: Jasmonate-Responsive Transcription Factors and a Conceptual Model for the Evolution of Metabolic Pathways.Frontiers in plant science · 2019Review
- An Open-Source, Programmable Pneumatic Setup for Operation and Automated Control of Single- and Multi-Layer Microfluidic Devices.HardwareX · 2018Article
- A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR-Dependent Mechanism for Stomatal Development.Plant physiology · 2017Article
- Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans.Human molecular genetics · 2017Article
- Article
- Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway.eLife · 2017Article
- Mechanisms of transcription factor evolution in Metazoa.Nucleic acids research · 2016Article
- Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.The Journal of biological chemistry · 2016Article
- Epistatic Interactions in the Arabinose Cis-Regulatory Element.Molecular biology and evolution · 2016Article
- Dry and wet approaches for genome-wide functional annotation of conventional and unconventional transcriptional activators.Computational and structural biotechnology journal · 2016Review
- Mechanisms of mutational robustness in transcriptional regulation.Frontiers in genetics · 2015Review
- Using protein-binding microarrays to study transcription factor specificity: homologs, isoforms and complexes.Briefings in functional genomics · 2015Review
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2 authors.
Funding
Abstract
Sequence-specific binding of a transcription factor to DNA is the central event in any transcriptional regulatory network. However, relatively little is known about the evolutionary plasticity of transcription factors. For example, the exact functional consequence of an amino acid substitution on the DNA-binding specificity of most transcription factors is currently not predictable. Furthermore, although the major structural families of transcription factors have been identified, the detailed DNA-binding repertoires within most families have not been characterized. We studied the sequence recognition code and evolvability of the basic helix-loop-helix transcription factor family by creating all possible 95 single-point mutations of five DNA-contacting residues of Max, a human helix-loop-helix transcription factor and measured the detailed DNA-binding repertoire of each mutant. Our results show that the sequence-specific repertoire of Max accessible through single-point mutations is extremely limited, and we are able to predict 92% of the naturally occurring diversity at these positions. All naturally occurring basic regions were also found to be accessible through functional intermediates. Finally, we observed a set of amino acids that are functional in vitro but are not found to be used naturally, indicating that functionality alone is not sufficient for selection.
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