ArticlePLoS genetics2012
Probing the informational and regulatory plasticity of a transcription factor DNA-binding domain.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The role of promiscuous molecular recognition in the evolution of RNase-based self-incompatibility in plants.Nature communications · 2024Article
- Disparate Dynamics of Gene Body andPlants (Basel, Switzerland) · 2021Article
- Experimental determination of evolutionary barriers to horizontal gene transfer.BMC microbiology · 2020Article
- Promoter Architecture and Promoter Engineering inMetabolites · 2020Review
- The relation between crosstalk and gene regulation form revisited.PLoS computational biology · 2020Article
- Recent insights into the genotype-phenotype relationship from massively parallel genetic assays.Evolutionary applications · 2019Review
- Mapping DNA sequence to transcription factor binding energy in vivo.PLoS computational biology · 2019Article
- Article
- Evolution of new regulatory functions on biophysically realistic fitness landscapes.Nature communications · 2017Article
- Article
- Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.The Journal of biological chemistry · 2016Article
- When the Scaffold Cannot Be Ignored: The Role of the Hydrophobic Core in Ligand Binding and Specificity.Journal of molecular biology · 2015Article
- An evolutionary perspective on protein moonlighting.Biochemical Society transactions · 2014Review
- Hybrid incompatibility arises in a sequence-based bioenergetic model of transcription factor binding.Genetics · 2014Article
- Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification.Genome research · 2014Article
- iSLIM: a comprehensive approach to mapping and characterizing gene regulatory networks.Nucleic acids research · 2013Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Transcription factors have two functional constraints on their evolution: (1) their binding sites must have enough information to be distinguishable from all other sequences in the genome, and (2) they must bind these sites with an affinity that appropriately modulates the rate of transcription. Since both are determined by the biophysical properties of the DNA-binding domain, selection on one will ultimately affect the other. We were interested in understanding how plastic the informational and regulatory properties of a transcription factor are and how transcription factors evolve to balance these constraints. To study this, we developed an in vivo selection system in Escherichia coli to identify variants of the helix-turn-helix transcription factor MarA that bind different sets of binding sites with varying degrees of degeneracy. Unlike previous in vitro methods used to identify novel DNA binders and to probe the plasticity of the binding domain, our selections were done within the context of the initiation complex, selecting for both specific binding within the genome and for a physiologically significant strength of interaction to maintain function of the factor. Using MITOMI, quantitative PCR, and a binding site fitness assay, we characterized the binding, function, and fitness of some of these variants. We observed that a large range of binding preferences, information contents, and activities could be accessed with a few mutations, suggesting that transcriptional regulatory networks are highly adaptable and expandable.
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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.