Stochastic resonances in a distributed genetic broadcasting system: the NF<i>κ</i>B/I<i>κ</i>B paradigm.

Abstract

Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites. Taking the genetic regulatory network of NF<i>κ</i>B as an exemplary system we explore the impact of having numerous distributed sites on the stochastic dynamics of oscillatory broadcasting genetic networks pointing out how resonances in binding cycles control the network's specificity and performance. We also show that active kinetic regulation of binding and unbinding through molecular stripping of DNA bound transcription factors can lead to a higher coherence of gene-co-expression and synchronous clearance.