Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation
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Published version
Author(s)
Type
Journal Article
Abstract
The differentiation of self-renewingprogenitor cells requires not only the regulation of lineage-and developmental stage-specific genes, but also the coordinated adaptation of housekeeping functionsfrom a metabolically active, proliferative state towards quiescence. How metabolic and cell cycle states are coordinated with the regulation of cell type-specific genes is an important question, as 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 expressionrequires afeedforward circuit whereby Ikarosdownregulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping statescan be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.
Date Issued
2019-04-12
Date Acceptance
2019-01-16
Citation
PLoS Biology, 2019, 17 (4)
ISSN
1544-9173
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Biology
Volume
17
Issue
4
Copyright Statement
© 2019 Ferreirós-Vidal et al. 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.
Sponsor
Wellcome Trust
Grant Number
099276/Z/12/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
ACUTE LYMPHOBLASTIC-LEUKEMIA
IKAROS
PROLIFERATION
NETWORK
CHILDHOOD
DELETION
DYNAMICS
CYCLE
IDENTIFICATION
SIGNATURE
06 Biological Sciences
11 Medical and Health Sciences
07 Agricultural and Veterinary Sciences
Developmental Biology
Publication Status
Published
Article Number
ARTN e2006506