Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation Journal Article

Author(s): Cepeda Humerez, Sarah A; Rieckh, Georg; Tkačik, Gašper
Article Title: Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation
Affiliation IST Austria
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.
Keywords: Gene Expression; Genes; Information Theory; Transcription; steady state; Thermodynamic model; Transcriptional regulation; Stochastic systems; Economic and social effects; Covalent modifications; Equilibrium models; Non equilibrium; Poisson noise; Trade off; Gen expression regulation
Journal Title: Physical Review Letters
Volume: 115
Issue 24
ISSN: 1079-7114
Publisher: American Physical Society  
Date Published: 2015-12-08
Start Page: Article number: 248101
Sponsor: G. R. acknowledges support from ERC Advanced Grant No. 250152.
DOI: 10.1103/PhysRevLett.115.248101
Notes: We thank TR Sokolowski and T Friedlander for helpful comments on the manuscript, and E van Nimwegen for suggesting that histone modification / remodeling might also constitute a candidate proofreading mechanism.
Open access: yes (repository)
IST Austria Authors
  1. Gasper Tkacik
    67 Tkacik
  2. Georg Rieckh
    5 Rieckh
Related IST Austria Work