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Intrinsic limits to gene regulation by global crosstalk | Plant Sciences and Genetics in Agriculture

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Intrinsic limits to gene regulation by global crosstalk

Citation:

Friedlander, T. ; Prizak, R. ; Guet, C. C. ; Barton, N. H. ; Tkačik, G. . Intrinsic Limits To Gene Regulation By Global Crosstalk. 2016, 7, 12307.

Date Published:

2016

Abstract:

Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.

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