title: Cross talk and interference enhance information capacity of a signaling pathway.
abstract: A recurring motif in gene regulatory networks is transcription factors (TFs) that regulate each other and then bind to overlapping sites on DNA, where they interact and synergistically control transcription of a target gene. Here, we suggest that this motif maximizes information flow in a noisy network. Gene expression is an inherently noisy process due to thermal fluctuations and the small number of molecules involved. A consequence of multiple TFs interacting at overlapping binding sites is that their binding noise becomes correlated. Using concepts from information theory, we show that in general a signaling pathway transmits more information if 1), noise of one input is correlated with that of the other; and 2), input signals are not chosen independently. In the case of TFs, the latter criterion hints at upstream cross-regulation. We demonstrate these ideas for competing TFs and feed-forward gene-regulatory modules, and discuss generalizations to other signaling pathways. Our results challenge the conventional approach of treating biological noise as uncorrelated fluctuations, and present a systematic method for understanding TF cross-regulation networks either from direct measurements of binding noise or from bioinformatic analysis of overlapping binding sites.
authors.affiliation: Kavli Institute for Theoretical Physics, University of California-Santa Barbara, Santa Barbara, California, USA. hormoz@kitp.ucsb.edu
authors.forename: Sahand
authors.initials: S
authors.lastname: Hormoz
mesh_terms: D001665:Binding Sites; D053263:Gene Regulatory Networks; D007257:Information Theory; D008954:Models, Biological; D015398:Signal Transduction; D059629:Signal-To-Noise Ratio; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors