title: The transcription factor titration effect dictates level of gene expression.
abstract: Models of transcription are often built around a picture of RNA polymerase and transcription factors (TFs) acting on a single copy of a promoter. However, most TFs are shared between multiple genes with varying binding affinities. Beyond that, genes often exist at high copy number-in multiple identical copies on the chromosome or on plasmids or viral vectors with copy numbers in the hundreds. Using a thermodynamic model, we characterize the interplay between TF copy number and the demand for that TF. We demonstrate the parameter-free predictive power of this model as a function of the copy number of the TF and the number and affinities of the available specific binding sites; such predictive control is important for the understanding of transcription and the desire to quantitatively design the output of genetic circuits. Finally, we use these experiments to dynamically measure plasmid copy number through the cell cycle.
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brewster
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Franz M
authors.initials: FM
authors.lastname: Weinert
authors.affiliation: Department of Physics, Princeton University, NJ 08540, USA.
authors.forename: Hernan G
authors.initials: HG
authors.lastname: Garcia
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Biophysics Program, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rydenfelt
authors.affiliation: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA; Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: phillips@pboc.caltech.edu.
authors.forename: Rob
authors.initials: R
authors.lastname: Phillips
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013816:Thermodynamics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors