Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation
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.
Code (0)
등록된 구현이 없습니다.
Tasks
SpecificitySimilar Papers 제목 키워드 기반
Competing endogenous RNA crosstalk at system level
microRNAs (miRNAs) regulate gene expression at post-transcriptional level by repressing target RNA molecules. Competition to bind miRNAs tends in turn to correlate their targets, establishing effective RNA-RNA interactio…
Timing consistency of T cell receptor activation in a stochastic model combining kinetic segregation and proofreading
T cell receptor signaling must operate reliably under tight time constraints. While assuming quite different mechanisms, two prominent models of T cell receptor activation, kinetic segregation and kinetic proofreading, b…
Receptor crosstalk improves concentration sensing of multiple ligands
Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems…
Translating ceRNA susceptibilities into correlation functions
Competition to bind microRNAs induces an effective positive crosstalk between their targets, therefore known as `competing endogenous RNAs' or ceRNAs. While such an effect is known to play a significant role in specific …
Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies
Cellular signaling, crucial for biological processes like immune response and homeostasis, relies on specificity and fidelity in signal transduction to accurately respond to stimuli amidst biological noise. Kinetic proof…
Specificity