Inaccessible LCG Promoters Act as Safeguards to Restrict T Cell Development to Appropriate Notch Signaling Environments.

Animals CpG Islands / genetics DNA / metabolism Deoxyribonuclease I / metabolism Mice, Inbred C57BL Promoter Regions, Genetic / genetics Receptors, Notch / metabolism Signal Transduction T-Lymphocytes / metabolism
DNA accessibility LCG promoters Notch T cell development

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
13 04 2021
Historique:
received: 10 07 2020
revised: 19 02 2021
accepted: 23 02 2021
pubmed: 27 3 2021
medline: 3 3 2022
entrez: 26 3 2021
Statut: ppublish

Résumé

T cell development is restricted to the thymus and is dependent on high levels of Notch signaling induced within the thymic microenvironment. To understand Notch function in thymic restriction, we investigated the basis for target gene selectivity in response to quantitative differences in Notch signal strength, focusing on the chromatin architecture of genes essential for T cell differentiation. We find that high Notch signal strength is required to activate promoters of known targets essential for T cell commitment, including Il2ra, Cd3ε, and Rag1, which feature low CpG content (LCG) and DNA inaccessibility in hematopoietic stem progenitor cells. Our findings suggest that promoter DNA inaccessibility at LCG T lineage genes provides robust protection against stochastic activation in inappropriate Notch signaling contexts, limiting T cell development to the thymus.

Identifiants

DOI: 10.1016/j.stemcr.2021.02.017 PMID: 33770495 PMC: PMC8072033
pubmed: 33770495
pii: S2213-6711(21)00097-7
doi: 10.1016/j.stemcr.2021.02.017
pmc: PMC8072033
pii:
doi:

Substances chimiques

Receptors, Notch 0
DNA 9007-49-2
Deoxyribonuclease I EC 3.1.21.1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

717-726

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK110563
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL100395
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Suzanne Furuyama (S)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Qian Vicky Wu (QV)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Barbara Varnum-Finney (B)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Richard Sandstrom (R)

Altius Institute for Biomedical Sciences, Seattle, WA 98121, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

Wouter Meuleman (W)

Altius Institute for Biomedical Sciences, Seattle, WA 98121, USA.

John A Stamatoyannopoulos (JA)

Altius Institute for Biomedical Sciences, Seattle, WA 98121, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Medicine, Division of Oncology, University of Washington, Seattle, WA 98195, USA.

Irwin D Bernstein (ID)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Washington, Seattle, WA 98195, USA. Electronic address: ibernste@fredhutch.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Désoxyribonucléases › Deoxyribonuclease I › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs Notch › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Inaccessible LCG Promoters Act as Safeguards...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Inaccessible LCG Promoters Act as Safeguards...