title: The Soft Touch: Low-Affinity Transcription Factor Binding Sites in Development and Evolution.
abstract: Transcription factor proteins regulate gene expression by binding to specific DNA regions. Most studies of transcription factor binding sites have focused on the highest affinity sites for each factor. There is abundant evidence, however, that binding sites with a range of affinities, including very low affinities, are critical to gene regulation. Here, we present the theoretical and experimental evidence for the importance of low-affinity sites in gene regulation and development. We also discuss the implications of the widespread use of low-affinity sites in eukaryotic genomes for robustness, precision, specificity, and evolution of gene regulation.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Crocker
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
authors.forename: Ella Preger-Ben
authors.initials: EP
authors.lastname: Noon
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA. Electronic address: sternd@janelia.hhmi.org.
authors.forename: David L
authors.initials: DL
authors.lastname: Stern
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D015509:Developmental Biology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D004247:DNA
keywords: Enhancer; Low-affinity binding sites; Protein–DNA interaction; Transcription factor; Transcription regulation; cis-Regulatory element