title: A quantitative understanding of lac repressor's binding specificity and flexibility.
abstract: Lac repressor, the first discovered transcriptional regulator, has been shown to confer multiple-modes of binding to its operator sites depending on the central spacer length. Other homolog members in the LacI/GalR family (PurR and YcjW) cannot bind their operator sites with similar structural flexibility. To decipher the underlying mechanism for this unique property, we used Spec-seq approach combined with site-directed mutagenesis to quantify the DNA binding specificity of multiple hybrids of lacI and PurR. We find that lac repressor's recognition di-residues YQ and its hinge helix loop regions are both critical for its structural flexibility. Also, specificity profiling of the whole lac operator suggests that a simple additive model from single variants suffice to predict other multivariant sites' energy reasonably well, and the genome occupancy model based on this specificity data correlates well within vivolac repressor binding profile.
authors.affiliation: Department of Genetics and Center for Genomic Sciences and Systems Biology, School of Medicine, Washington University, St. Louis, MO 63108, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Genetics and Center for Genomic Sciences and Systems Biology, School of Medicine, Washington University, St. Louis, MO 63108, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Genetics and Center for Genomic Sciences and Systems Biology, School of Medicine, Washington University, St. Louis, MO 63108, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stormo
keywords: Spec-seq; binding flexibility; ionic strength; lac repressor