RT Journal Article
SR Electronic
T1 Stochastic dynamics of genetic broadcasting networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 074401
DO 10.1101/074401
A1 Davit A. Potoyan
A1 Peter G. Wolynes
YR 2016
UL http://biorxiv.org/content/early/2016/09/09/074401.abstract
AB 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” of master genes that broadcast their signals to large number of binding sites. We demonstrate that this “time-scale crisis” can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying 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.