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Thermodynamic model of gene regulation for the Or59b olfactory receptor in Drosophila
Linköping University, Department of Electrical Engineering. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
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2019 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 1, article id e1006709Article in journal (Refereed) Published
Abstract [en]

Complex eukaryotic promoters normally contain multiple cis-regulatory sequences for different transcription factors (TFs). The binding patterns of the TFs to these sites, as well as the way the TFs interact with each other and with the RNA polymerase (RNAp), lead to combinatorial problems rarely understood in detail, especially under varying epigenetic conditions. The aim of this paper is to build a model describing how the main regulatory cluster of the olfactory receptor Or59b drives transcription of this gene in Drosophila. The cluster-driven expression of this gene is represented as the equilibrium probability of RNAp being bound to the promoter region, using a statistical thermodynamic approach. The RNAp equilibrium probability is computed in terms of the occupancy probabilities of the single TFs of the cluster to the corresponding binding sites, and of the interaction rules among TFs and RNAp, using experimental data of Or59b expression to tune the model parameters. The model reproduces correctly the changes in RNAp binding probability induced by various mutation of specific sites and epigenetic modifications. Some of its predictions have also been validated in novel experiments.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2019. Vol. 15, no 1, article id e1006709
National Category
Bioinformatics and Systems Biology
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URN: urn:nbn:se:liu:diva-154703DOI: 10.1371/journal.pcbi.1006709ISI: 000457372500037PubMedID: 30653495OAI: oai:DiVA.org:liu-154703DiVA, id: diva2:1292631
Note

Funding Agencies|Swedish Research Council (VR) [2016-06726]; Swedish Foundation for Strategic Research (SSF) [SB16-0011]

Available from: 2019-02-28 Created: 2019-02-28 Last updated: 2019-03-15

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Gonzalez Bosca, AlejandraJafari, ShadiZenere, AlbertoAlenius, MattiasAltafini, Claudio
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