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Determination of the gene regulatory network of a genome-reduced bacterium highlights alternative regulation independent of transcription factors

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dc.contributor.author Yus, Eva
dc.contributor.author Lloréns Rico, Verónica, 1989-
dc.contributor.author Martínez, Sira
dc.contributor.author Gallo López, Carolina, 1984-
dc.contributor.author Eilers, Hinnerk
dc.contributor.author Blötz, Cedric
dc.contributor.author Stülke, Jörg
dc.contributor.author Lluch-Senar, Maria 1982-
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.date.accessioned 2019-10-29T10:59:59Z
dc.date.available 2019-10-29T10:59:59Z
dc.date.issued 2019
dc.identifier.citation Yus E, Lloréns-Rico V, Martínez S, Gallo C, Eilers H, Blötz C, Stülke J, Lluch-Senar M, Serrano L. Determination of the gene regulatory network of a genome-reduced bacterium highlights alternative regulation independent of transcription factors. Cell Syst. 2019; 9(2):143-158.e13. DOI 10.1016/j.cels.2019.07.001
dc.identifier.issn 2405-4720
dc.identifier.uri http://hdl.handle.net/10230/42545
dc.description.abstract Here, we determined the relative importance of different transcriptional mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae, by employing an array of experimental techniques under multiple genetic and environmental perturbations. Of the 143 genes tested (21% of the bacterium's annotated proteins), only 55% showed an altered phenotype, highlighting the robustness of biological systems. We identified nine transcription factors (TFs) and their targets, representing 43% of the genome, and 16 regulators that indirectly affect transcription. Only 20% of transcriptional regulation is mediated by canonical TFs when responding to perturbations. Using a Random Forest, we quantified the non-redundant contribution of different mechanisms such as supercoiling, metabolic control, RNA degradation, and chromosome topology to transcriptional changes. Model-predicted gene changes correlate well with experimental data in 95% of the tested perturbations, explaining up to 70% of the total variance when also considering noise. This analysis highlights the importance of considering non-TF-mediated regulation when engineering bacteria.
dc.description.sponsorship The project was supported by funds from the Fundación Marcelino Botín and the Spanish Ministerio de Economía y Competitividad (BIO2007-61762). This project was financed by Instituto de Salud Carlos III and co-financed by Federación Española de Enfermedades Raras under grant agreement PI10/01702 and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, under grant agreements no 634942 (MycoSynVac) and 670216 (MYCOCHASSIS). We acknowledge support from the Spanish Ministry of Economy and Competitiveness to the EMBL partnership, Centro de Excelencia Severo Ochoa.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Syst. 2019; 9(2):143-158.e13
dc.rights © 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Determination of the gene regulatory network of a genome-reduced bacterium highlights alternative regulation independent of transcription factors
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.cels.2019.07.001
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BIO2007-61762
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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