TY - JOUR
T1 - Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
AU - Ferreirós-Vidal, Isabel
AU - Carroll, Thomas
AU - Zhang, Tianyi
AU - Lagani, Vincenzo
AU - Ramirez, Ricardo N.
AU - Ing-Simmons, Elizabeth
AU - Gómez-Valadés, Alicia G.
AU - Cooper, Lee
AU - Liang, Ziwei
AU - Papoutsoglou, Georgios
AU - Dharmalingam, Gopuraja
AU - Guo, Ya
AU - Tarazona, Sonia
AU - Fernandes, Sunjay J.
AU - Noori, Peri
AU - Silberberg, Gilad
AU - Fisher, Amanda G.
AU - Tsamardinos, Ioannis
AU - Mortazavi, Ali
AU - Lenhard, Boris
AU - Conesa, Ana
AU - Tegner, Jesper
AU - Merkenschlager, Matthias
AU - Gomez-Cabrero, David
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: EU 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.
PY - 2019/4/12
Y1 - 2019/4/12
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/652916
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006506
UR - http://www.scopus.com/inward/record.url?scp=85065217452&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.2006506
DO - 10.1371/journal.pbio.2006506
M3 - Article
C2 - 30978178
SN - 1545-7885
VL - 17
SP - e2006506
JO - PLOS Biology
JF - PLOS Biology
IS - 4
ER -
