Promoter activity buffering reduces the fitness cost of misregulation

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• dc.contributor.author Schikora Tamarit, Miquel Àngelca
• dc.contributor.author López-Grado i Salinas, Guillemca
• dc.contributor.author González Navasa, Carolinaca
• dc.contributor.author Calderón, Ireneca
• dc.contributor.author Marcos Fa, Xavica
• dc.contributor.author Sas, Miquelca
• dc.contributor.author Carey, Lucas, 1980-ca
• dc.date.accessioned 2018-07-19T09:06:48Z
• dc.date.available 2018-07-19T09:06:48Z
• dc.date.issued 2018
• dc.description.abstract Organisms regulate gene expression through changes in the activity of transcription factors (TFs). In yeast, the response of genes to changes in TF activity is generally assumed to be encoded in the promoter. To directly test this assumption, we chose 42 genes and, for each, replaced the promoter with a synthetic inducible promoter and measured how protein expression changes as a function of TF activity. Most genes exhibited gene-specific TF dose-response curves not due to differences in mRNA stability, translation, or protein stability. Instead, most genes have an intrinsic ability to buffer the effects of promoter activity. This can be encoded in the open reading frame and the 3' end of genes and can be implemented by both autoregulatory feedback and by titration of limiting trans regulators. We show experimentally and computationally that, when misexpression of a gene is deleterious, this buffering insulates cells from fitness defects due to misregulation
• dc.description.sponsorship L.B.C. was supported by Ministerio de Economía y Competitividad (MINECO) and the Fondo Europeo de Desarrollo Regional (FEDER) (BFU2015-68351-P), AGAUR (2014SGR0974 and 2017SGR1054), and the Unidad de Excelencia María de Maeztu, funded by MINECO (MDM-2014-0370). We would like to thank the UPF/CRG Flow Cytometry core.
• dc.format.mimetype application/pdf
• dc.identifier.citation Schikora-Tamarit MÀ, Lopez-Grado i Salinas G, Gonzalez-Navasa C, Calderón I, Marcos-Fa X, Sas M et al. Promoter Activity Buffering Reduces the Fitness Cost of Misregulation. Cell Reports. 2018;24(3):755-65. DOI: 10.1016/j.celrep.2018.06.059
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2018.06.059
• dc.identifier.issn 2211-1247
• dc.identifier.uri http://hdl.handle.net/10230/35202
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Cell Reports. 2018;24(3):755-65
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68351-P
• dc.rights © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Feedback
• dc.subject.keyword Fitness
• dc.subject.keyword Gene expression
• dc.subject.keyword Mathematical modeling
• dc.subject.keyword Systems biology
• dc.subject.keyword Transcription
• dc.subject.keyword Yeast
• dc.title Promoter activity buffering reduces the fitness cost of misregulationca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion