Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation

S.A. Cepeda Humerez, G. Rieckh, G. Tkacik, Physical Review Letters 115 (2015).


Journal Article | Published | English
Department
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.
Publishing Year
Date Published
2015-12-08
Journal Title
Physical Review Letters
Volume
115
Issue
24
Article Number
248101
IST-REx-ID

Cite this

Cepeda Humerez SA, Rieckh G, Tkacik G. Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. Physical Review Letters. 2015;115(24). doi:10.1103/PhysRevLett.115.248101
Cepeda Humerez, S. A., Rieckh, G., & Tkacik, G. (2015). Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. Physical Review Letters, 115(24). https://doi.org/10.1103/PhysRevLett.115.248101
Cepeda Humerez, Sarah A, Georg Rieckh, and Gasper Tkacik. “Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.” Physical Review Letters 115, no. 24 (2015). https://doi.org/10.1103/PhysRevLett.115.248101.
S. A. Cepeda Humerez, G. Rieckh, and G. Tkacik, “Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation,” Physical Review Letters, vol. 115, no. 24, 2015.
Cepeda Humerez SA, Rieckh G, Tkacik G. 2015. Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. Physical Review Letters. 115(24).
Cepeda Humerez, Sarah A., et al. “Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.” Physical Review Letters, vol. 115, no. 24, 248101, American Physical Society, 2015, doi:10.1103/PhysRevLett.115.248101.

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