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 .
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, 2) input signals are not chosen independently. In the case of TFs, the latter criterion hints at up-stream 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 bioinformatic analysis of overlapping binding-sites .
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binding sites
binding-sites
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,
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in general
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the
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and
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the
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explicitly
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the toy model of two TFs competing for the same binding site. We suggest that this mechanism potentially explains the motif of a coherent
competing TFs and
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loop terminating in overlapping binding sites commonly found in developmental networks
gene regulatory modules
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three specific examples. The systematic method proposed herein can be used to shed light on
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
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binding sites
binding-sites