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Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation

The 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 sta...

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Autores principales: Ferreirós-Vidal, Isabel, Carroll, Thomas, Zhang, Tianyi, Lagani, Vincenzo, Ramirez, Ricardo N., Ing-Simmons, Elizabeth, Gómez-Valadés, Alicia G., Cooper, Lee, Liang, Ziwei, Papoutsoglou, Georgios, Dharmalingam, Gopuraja, Guo, Ya, Tarazona, Sonia, Fernandes, Sunjay J., Noori, Peri, Silberberg, Gilad, Fisher, Amanda G., Tsamardinos, Ioannis, Mortazavi, Ali, Lenhard, Boris, Conesa, Ana, Tegner, Jesper, Merkenschlager, Matthias, Gomez-Cabrero, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481923/
https://www.ncbi.nlm.nih.gov/pubmed/30978178
http://dx.doi.org/10.1371/journal.pbio.2006506
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author Ferreirós-Vidal, Isabel
Carroll, Thomas
Zhang, Tianyi
Lagani, Vincenzo
Ramirez, Ricardo N.
Ing-Simmons, Elizabeth
Gómez-Valadés, Alicia G.
Cooper, Lee
Liang, Ziwei
Papoutsoglou, Georgios
Dharmalingam, Gopuraja
Guo, Ya
Tarazona, Sonia
Fernandes, Sunjay J.
Noori, Peri
Silberberg, Gilad
Fisher, Amanda G.
Tsamardinos, Ioannis
Mortazavi, Ali
Lenhard, Boris
Conesa, Ana
Tegner, Jesper
Merkenschlager, Matthias
Gomez-Cabrero, David
author_facet Ferreirós-Vidal, Isabel
Carroll, Thomas
Zhang, Tianyi
Lagani, Vincenzo
Ramirez, Ricardo N.
Ing-Simmons, Elizabeth
Gómez-Valadés, Alicia G.
Cooper, Lee
Liang, Ziwei
Papoutsoglou, Georgios
Dharmalingam, Gopuraja
Guo, Ya
Tarazona, Sonia
Fernandes, Sunjay J.
Noori, Peri
Silberberg, Gilad
Fisher, Amanda G.
Tsamardinos, Ioannis
Mortazavi, Ali
Lenhard, Boris
Conesa, Ana
Tegner, Jesper
Merkenschlager, Matthias
Gomez-Cabrero, David
author_sort Ferreirós-Vidal, Isabel
collection PubMed
description The 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.
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spelling pubmed-64819232019-05-07 Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation Ferreirós-Vidal, Isabel Carroll, Thomas Zhang, Tianyi Lagani, Vincenzo Ramirez, Ricardo N. Ing-Simmons, Elizabeth Gómez-Valadés, Alicia G. Cooper, Lee Liang, Ziwei Papoutsoglou, Georgios Dharmalingam, Gopuraja Guo, Ya Tarazona, Sonia Fernandes, Sunjay J. Noori, Peri Silberberg, Gilad Fisher, Amanda G. Tsamardinos, Ioannis Mortazavi, Ali Lenhard, Boris Conesa, Ana Tegner, Jesper Merkenschlager, Matthias Gomez-Cabrero, David PLoS Biol Research Article The 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. Public Library of Science 2019-04-12 /pmc/articles/PMC6481923/ /pubmed/30978178 http://dx.doi.org/10.1371/journal.pbio.2006506 Text en © 2019 Ferreirós-Vidal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ferreirós-Vidal, Isabel
Carroll, Thomas
Zhang, Tianyi
Lagani, Vincenzo
Ramirez, Ricardo N.
Ing-Simmons, Elizabeth
Gómez-Valadés, Alicia G.
Cooper, Lee
Liang, Ziwei
Papoutsoglou, Georgios
Dharmalingam, Gopuraja
Guo, Ya
Tarazona, Sonia
Fernandes, Sunjay J.
Noori, Peri
Silberberg, Gilad
Fisher, Amanda G.
Tsamardinos, Ioannis
Mortazavi, Ali
Lenhard, Boris
Conesa, Ana
Tegner, Jesper
Merkenschlager, Matthias
Gomez-Cabrero, David
Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title_full Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title_fullStr Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title_full_unstemmed Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title_short Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
title_sort feedforward regulation of myc coordinates lineage-specific with housekeeping gene expression during b cell progenitor cell differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481923/
https://www.ncbi.nlm.nih.gov/pubmed/30978178
http://dx.doi.org/10.1371/journal.pbio.2006506
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