title: Cell-to-cell variability in the propensity to transcribe explains correlated fluctuations in gene expression.
abstract: Random fluctuations in gene expression lead to wide cell-to-cell differences in RNA and protein counts. Most efforts to understand stochastic gene expression focus on local (intrinisic) fluctuations, which have an exact theoretical representation. However, no framework exists to model global (extrinsic) mechanisms of stochasticity. We address this problem by dissecting the sources of stochasticity that influence the expression of a yeast heat shock gene, SSA1. Our observations suggest that extrinsic stochasticity does not influence every step of gene expression, but rather arises specifically from cell-to-cell differences in the propensity to transcribe RNA. This led us to propose a framework for stochastic gene expression where transcription rates vary globally in combination with local, gene-specific fluctuations in all steps of gene expression. The proposed model better explains total expression stochasticity than the prevailing ON-OFF model and offers transcription as the specific mechanism underlying correlated fluctuations in gene expression.
authors.affiliation: Computational and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, United States. ; Center for Genome Sciences, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sherman
authors.affiliation: Center for Genome Sciences, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States.
authors.forename: Kim
authors.initials: K
authors.lastname: Lorenz
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: M Hunter
authors.initials: MH
authors.lastname: Lanier
authors.affiliation: Center for Genome Sciences, Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States.
authors.forename: Barak A
authors.initials: BA
authors.lastname: Cohen