Gene Regulatory Strategies that Decode the Duration of NFκB Dynamics Contribute to LPS- versus TNF-Specific Gene Expression.

Gene Expression / genetics Gene Expression Regulation / genetics Humans Lipopolysaccharides / metabolism NF-kappa B / metabolism
NF-kappa B chromatin regulation duration decoding mRNA half-life stimulus-specificity

Journal

Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080

Informations de publication

Date de publication:
26 02 2020
Historique:
received: 05 04 2019
revised: 20 08 2019
accepted: 23 12 2019
pubmed: 24 1 2020
medline: 25 5 2021
entrez: 24 1 2020
Statut: ppublish

Résumé

Pathogen-derived lipopolysaccharide (LPS) and cytokine tumor necrosis factor (TNF) activate NFκB with distinct duration dynamics, but how immune response genes decode NFκB duration to produce stimulus-specific expression remains unclear. Here, detailed transcriptomic profiling of combinatorial and temporal control mutants identified 81 genes that depend on stimulus-specific NFκB duration for their stimulus-specificity. Combining quantitative experimentation with mathematical modeling, we found that for some genes a long mRNA half-life allowed effective decoding, but for many genes this was insufficient to account for the data; instead, we found that chromatin mechanisms, such as a slow transition rate between inactive and RelA-bound enhancer states, could also decode NFκB dynamics. Chromatin-mediated decoding is favored by genes acting as immune effectors (e.g., tissue remodelers and T cell recruiters) rather than immune regulators (e.g., signaling proteins and monocyte recruiters). Overall, our results delineate two gene regulatory strategies that decode stimulus-specific NFκB dynamics and determine distinct biological functions.

Identifiants

DOI: 10.1016/j.cels.2019.12.004 PMID: 31972132 PMC: PMC7047529
pubmed: 31972132
pii: S2405-4712(19)30465-X
doi: 10.1016/j.cels.2019.12.004
pmc: PMC7047529
mid: NIHMS1551661
pii:
doi:

Substances chimiques

Lipopolysaccharides 0
NF-kappa B 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

169-182.e5

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI127864
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132835
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117134
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008042
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Supriya Sen (S)

Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA 90095, USA.

Zhang Cheng (Z)

Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences (QCB), University of California, Los Angeles, Los Angeles, CA 90095, USA.

Katherine M Sheu (KM)

Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA 90095, USA.

Yu Hsin Chen (YH)

Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA 90095, USA.

Alexander Hoffmann (A)

Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences (QCB), University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ahoffmann@ucla.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Gene Regulatory Strategies that Decode the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Gene Regulatory Strategies that Decode the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Gene Regulatory Strategies that Decode the...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Gene Regulatory Strategies that Decode the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Gene Regulatory Strategies that Decode the...