title: Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.
abstract: Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that noncognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here, we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative nonequilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and predicts increased noise in gene expression as a trade-off for improved specificity. Using information theory, we quantify this trade-off to find when optimal proofreading architectures are favored over their equilibrium counterparts. Such architectures exhibit significant super-Poisson noise at low expression in steady state.
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Cepeda-Humerez
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Rieckh
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.
authors.forename: Gašper
authors.initials: G
authors.lastname: Tkačik
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008957:Models, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013269:Stochastic Processes; D013816:Thermodynamics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D004247:DNA