Transient Memory in Gene Regulation

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GUET, Calin, Thomas A. HENZINGER, Claudia IGLER, Tatjana PETROV, Ali SEZGIN, 2019. Transient Memory in Gene Regulation. 17th International Conference, CMSB 2019. Trieste, Italy, Sep 18, 2019 - Sep 20, 2019. In: BORTOLUSSI, Luca, ed., Guido SANGUINETTI, ed.. Computational Methods in Systems Biology : 17th International Conference, CMSB 2019, Trieste, Italy, September 18-20, 2019, proceedings. Cham:Springer, pp. 155-187. ISSN 0302-9743. eISSN 1611-3349. ISBN 978-3-030-31303-6. Available under: doi: 10.1007/978-3-030-31304-3_9

@inproceedings{Guet2019-09-17Trans-47051, title={Transient Memory in Gene Regulation}, year={2019}, doi={10.1007/978-3-030-31304-3_9}, number={11773}, isbn={978-3-030-31303-6}, issn={0302-9743}, address={Cham}, publisher={Springer}, series={Lecture Notes in Bioinformatics}, booktitle={Computational Methods in Systems Biology : 17th International Conference, CMSB 2019, Trieste, Italy, September 18-20, 2019, proceedings}, pages={155--187}, editor={Bortolussi, Luca and Sanguinetti, Guido}, author={Guet, Calin and Henzinger, Thomas A. and Igler, Claudia and Petrov, Tatjana and Sezgin, Ali} }

2019-09-27T07:37:00Z Henzinger, Thomas A. Petrov, Tatjana eng The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.<br /><br />In this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.<br /><br />The behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA , before applying rapid equilibrium assumptions. Igler, Claudia Petrov, Tatjana Transient Memory in Gene Regulation Guet, Calin Henzinger, Thomas A. 2019-09-17 2019-09-27T07:37:00Z Sezgin, Ali Guet, Calin Sezgin, Ali Igler, Claudia

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