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bioRxiv · 10.1101/192039

Distributed and dynamic intracellular organization of extracellular information

Granados, A. A.·Pietsch, J. M.·Cepeda-Humerez, S.·Tkacik, G.·Swain, P. S.
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Abstract

Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for ten transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: generalists (Msn2/4, Tod6/Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. Each transcription factor reports differently, and it is only their collective response that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change, and we predict that such multi-dimensional representations are common in cellular decision-making.\n\nSignificance StatementTo thrive in diverse environments, cells must represent extracellular change intracellularly despite stochastic biochemistry. Here we introduce a quantitative framework for investigating the organization of information within a cell. Combining single-cell measurements of intracellular dynamics with a new, scalable methodology for estimating mutual information between time-series and a discrete input, we demonstrate that extracellular information is encoded in the dynamics of the nuclear localization of transcription factors and that information is lost with alternative static statistics. Any one transcription factor is usually insufficient, but the collective dynamics of multiple transcription factors can represent complex extracellular change. We therefore show that a cells internal representation of its environment can be both distributed across diverse proteins and dynamically encoded.

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Granados, A. A., Pietsch, J. M., Cepeda-Humerez, S., Tkacik, G., Swain, P. S.. 2017-09-21. Distributed and dynamic intracellular organization of extracellular information. https://doi.org/10.1101/192039

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