Cross-talk and interference can enhance information capacity of a signaling pathway

Biology – Quantitative Biology – Molecular Networks

Scientific paper

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7 pages, 4 figures

Scientific paper

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 a signaling pathway transmits more information if 1) the noise of one input is correlated with that of the other, and 2) the input signals are not chosen independently. In the case of TFs, the latter criterion hints at up-stream cross-regulation. We explicitly demonstrate these ideas for the toy model of two TFs competing for the same binding site. We suggest that this mechanism potentially explains the motif of a coherent feed-forward loop terminating in overlapping binding sites commonly found in developmental networks, and discuss three specific examples. The systematic method proposed herein can be used to shed light on TF cross-regulation networks either from direct measurements of binding noise, or bioinformatic analysis of overlapping binding sites.

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