Stochastic dynamics of genetic broadcasting networks

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2017
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American Physical Society
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The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a “time-scale crisis” for master genes that broadcast their signals to a large number of binding sites. We demonstrate that this time-scale crisis for clearance in a large broadcasting network can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying a model of the stochastic dynamics of the genetic network of the central eukaryotic master regulator NFκB which broadcasts its signals to many downstream genes that regulate immune response, apoptosis, etc.

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Potoyan, Davit A. and Wolynes, Peter G.. "Stochastic dynamics of genetic broadcasting networks." Physical Review E, 96, no. 5 (2017) American Physical Society: https://doi.org/10.1103/PhysRevE.96.052305.

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