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dc.contributor.authorFerreirós-Vidal, Isabel
dc.contributor.authorCarroll, Thomas
dc.contributor.authorZhang, Tianyi
dc.contributor.authorLagani, Vincenzo
dc.contributor.authorRamirez, Ricardo N.
dc.contributor.authorIng-Simmons, Elizabeth
dc.contributor.authorGómez-Valadés, Alicia G.
dc.contributor.authorCooper, Lee
dc.contributor.authorLiang, Ziwei
dc.contributor.authorPapoutsoglou, Georgios
dc.contributor.authorDharmalingam, Gopuraja
dc.contributor.authorGuo, Ya
dc.contributor.authorTarazona, Sonia
dc.contributor.authorFernandes, Sunjay J.
dc.contributor.authorNoori, Peri
dc.contributor.authorSilberberg, Gilad
dc.contributor.authorFisher, Amanda G.
dc.contributor.authorTsamardinos, Ioannis
dc.contributor.authorMortazavi, Ali
dc.contributor.authorLenhard, Boris
dc.contributor.authorConesa, Ana
dc.contributor.authorTegner, Jesper
dc.contributor.authorMerkenschlager, Matthias
dc.contributor.authorGomez-Cabrero, David
dc.date.accessioned2019-05-20T08:59:22Z
dc.date.available2019-05-20T08:59:22Z
dc.date.issued2019-04-12
dc.identifier.citationFerreirós-Vidal I, Carroll T, Zhang T, Lagani V, Ramirez RN, et al. (2019) Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation. PLOS Biology 17: e2006506. Available: http://dx.doi.org/10.1371/journal.pbio.2006506.
dc.identifier.issn1545-7885
dc.identifier.doi10.1371/journal.pbio.2006506
dc.identifier.urihttp://hdl.handle.net/10754/652916
dc.description.abstractThe differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.
dc.description.sponsorshipEU FP7-Health STATegra project (grant number 36000). AG, VL, RR, AC, GP, ST, SF, PN, ME, JT, AM, MM, DGC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number 099276/Z/12/Z). MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medical Research Council, UK (grant number Institute Core Funding). AGF, BL, MM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bloodwise (grant number 09036). LC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wellcome (grant number). BL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number Repleniche). AGF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council (grant number 617393- CAUSALPATH). IT, VL, GP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MINECO (grant number BIO2015-71658-R). AC, ST. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.publisherPublic Library of Science (PLoS)
dc.relation.urlhttps://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006506
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleFeedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.identifier.journalPLOS Biology
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionMRC London Institute of Medical Sciences, London, , United Kingdom
dc.contributor.institutionInstitute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, , United Kingdom
dc.contributor.institutionLymphocyte Development Group, MRC London Institute of Medical Sciences, London, , United Kingdom
dc.contributor.institutionInstitute of Chemical Biology, Ilia State University, Tbilisi, Georgia
dc.contributor.institutionGnosis Data Analysis, Heraklion, , Greece
dc.contributor.institutionDepartment of Developmental and Cell Biology and Center for Complex Biological Systems, University of California, Irvine, CA, , United States
dc.contributor.institutionComputational Regulatory Genomics, MRC London Institute of Medical Sciences, London, , United Kingdom
dc.contributor.institutionComputer Science Department, University of Crete, Heraklion, , Greece
dc.contributor.institutionDepartment of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, , Spain
dc.contributor.institutionGenomics of Gene Expression Laboratory, Principe Felipe Research Center, Valencia, , Spain
dc.contributor.institutionUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, , Sweden
dc.contributor.institutionSars International Centre for Marine Molecular Biology, University of Bergen, Bergen, , Norway
dc.contributor.institutionMicrobiology and Cell Science Department, IFAS, University of Florida, Gainesville, FL, , United States
dc.contributor.institutionScience for Life Laboratory, Solna, , Sweden
dc.contributor.institutionNavarrabiomed, Complejo Hospitalario de Navarra (CHN), IdiSNA, Universidad Pública de Navarra (UPNA), Pamplona, , Spain
dc.contributor.institutionCentre for Host Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, , United Kingdom
kaust.personTegner, Jesper
refterms.dateFOA2019-05-20T12:49:55Z


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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.