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Promoter activity buffering reduces the fitness cost of misregulation

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dc.contributor.author Schikora Tamarit, Miquel Àngel
dc.contributor.author López-Grado i Salinas, Guillem
dc.contributor.author González Navasa, Carolina
dc.contributor.author Calderón, Irene
dc.contributor.author Marcos Fa, Xavi
dc.contributor.author Sas, Miquel
dc.contributor.author Carey, Lucas, 1980-
dc.date.accessioned 2018-07-19T09:06:48Z
dc.date.available 2018-07-19T09:06:48Z
dc.date.issued 2018
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.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/35202
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.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Reports. 2018;24(3):755-65
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.uri http://creativecommons.org/licenses/by/4.0/
dc.title Promoter activity buffering reduces the fitness cost of misregulation
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2018.06.059
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.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68351-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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