Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation

• Main Authors: Cepeda-Humerez, Sarah A, Rieckh, Georg, Tkačik, Gašper
• Format: Journal Article
• Language: English
• Published: 22-04-2015
• Subjects: Quantitative Biology - Molecular Networks
• DOI: 10.48550/arxiv.1504.05716

Phys. Rev. Lett. 115, 248101 (2015) 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 non-cognate 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
non-equilibrium scheme that implements kinetic proofreading to suppress
erroneous initiation. This proposal is consistent with the observed covalent
modifications of the transcriptional apparatus and would predict increased
noise in gene expression as a tradeoff for improved specificity. Using
information theory, we quantify this tradeoff to find when optimal proofreading
architectures are favored over their equilibrium counterparts.