title: Concentration- and chromosome-organization-dependent regulator unbinding from DNA for transcription regulation in living cells.
abstract: Binding and unbinding of transcription regulators at operator sites constitute a primary mechanism for gene regulation. While many cellular factors are known to regulate their binding, little is known on how cells can modulate their unbinding for regulation. Using nanometer-precision single-molecule tracking, we study the unbinding kinetics from DNA of two metal-sensing transcription regulators in living Escherichia coli cells. We find that they show unusual concentration-dependent unbinding kinetics from chromosomal recognition sites in both their apo and holo forms. Unexpectedly, their unbinding kinetics further varies with the extent of chromosome condensation, and more surprisingly, varies in opposite ways for their apo-repressor versus holo-activator forms. These findings suggest likely broadly relevant mechanisms for facile switching between transcription activation and deactivation in vivo and in coordinating transcription regulation of resistance genes with the cell cycle.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Tai-Yen
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Ace George
authors.initials: AG
authors.lastname: Santiago
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Won
authors.initials: W
authors.lastname: Jung
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Krzemiński
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Danya J
authors.initials: DJ
authors.lastname: Martell
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
mesh_terms: D002876:Chromosomes, Bacterial; D004269:DNA, Bacterial / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins