title: Quantitative influence of macromolecular crowding on gene regulation kinetics.
abstract: We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS Mw = 12.91 kDa) and 1550 s (e.g. for PepA6 of Mw = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are between for large proteins up to for small monomers or dimers. Three-dimensional diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D sliding coefficients, nevertheless the sliding enhances the binding rates of TF to specific sites by 1-2 orders of magnitude. The latter effect is due to ubiquitous non-specific binding. We compare the model to experimental data for LacI repressor and find that non-specific binding of the protein to DNA is activation- and not diffusion-limited. We show that the target location rate by LacI repressor is optimized with respect to microscopic rate constant for association to non-specific sites on DNA. We analyse the effect of oligomerization of TFs and DNA looping effects on searching kinetics. We show that optimal searching strategy depends on TF abundance.
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, 44/52 Kasprzaka, 01-224 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Tabaka
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kalwarczyk
authors.forename: Robert
authors.initials: R
authors.lastname: Hołyst
mesh_terms: D004269:DNA, Bacterial / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D056968:Lac Repressors / Q000378:metabolism; D008957:Models, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases