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


Journal

PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755

Informations de publication

Date de publication:
04 2019
Historique:
received: 29 04 2018
accepted: 16 03 2019
revised: 24 04 2019
pubmed: 13 4 2019
medline: 7 1 2020
entrez: 13 4 2019
Statut: epublish

Résumé

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.

Identifiants

pubmed: 30978178
doi: 10.1371/journal.pbio.2006506
pii: pbio.2006506
pmc: PMC6481923
doi:

Substances chimiques

Transcription Factors 0
Ikaros Transcription Factor 148971-36-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2006506

Subventions

Organisme : Medical Research Council
ID : MC_U120027516
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1102/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 099276/Z/12/Z
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Isabel Ferreirós-Vidal (I)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Thomas Carroll (T)

MRC London Institute of Medical Sciences, London, United Kingdom.

Tianyi Zhang (T)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Vincenzo Lagani (V)

Gnosis Data Analysis, Heraklion, Greece.
Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.

Ricardo N Ramirez (RN)

Department of Developmental and Cell Biology and Center for Complex Biological Systems, University of California, Irvine, California, United States of America.

Elizabeth Ing-Simmons (E)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.
Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London, United Kingdom.

Alicia G Gómez-Valadés (AG)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Lee Cooper (L)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Ziwei Liang (Z)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Georgios Papoutsoglou (G)

Computer Science Department, University of Crete, Heraklion, Greece.

Gopuraja Dharmalingam (G)

MRC London Institute of Medical Sciences, London, United Kingdom.

Ya Guo (Y)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Sonia Tarazona (S)

Genomics of Gene Expression Laboratory, Principe Felipe Research Center, Valencia, Spain.
Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain.

Sunjay J Fernandes (SJ)

Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Peri Noori (P)

Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Gilad Silberberg (G)

Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Amanda G Fisher (AG)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

Ioannis Tsamardinos (I)

Gnosis Data Analysis, Heraklion, Greece.
Computer Science Department, University of Crete, Heraklion, Greece.

Ali Mortazavi (A)

Department of Developmental and Cell Biology and Center for Complex Biological Systems, University of California, Irvine, California, United States of America.

Boris Lenhard (B)

Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.
Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London, United Kingdom.
Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen, Norway.

Ana Conesa (A)

Microbiology and Cell Science Department, IFAS, University of Florida, Gainesville, Florida, United States of America.

Jesper Tegner (J)

Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Solna, Sweden.
Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Saudi Arabia.

Matthias Merkenschlager (M)

Lymphocyte Development Group, MRC London Institute of Medical Sciences, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.

David Gomez-Cabrero (D)

Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Solna, Sweden.
Centre for Host Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom.
Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain.

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