A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV.
Cell Differentiation
Chromatin
/ metabolism
Dendritic Cells
/ metabolism
Female
Gene Expression Regulation
Gene Regulatory Networks
HEK293 Cells
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunity, Innate
/ genetics
Interferon Type I
/ metabolism
Male
Monocytes
/ metabolism
Promoter Regions, Genetic
/ genetics
Retinoic Acid Receptor alpha
/ metabolism
Transcription Factors
/ metabolism
Transcriptome
/ genetics
ATAC-seq
DNA sensing
IRF3
NF-κB
RNA-seq
STING
cGAS
chromatin modification
innate signaling
network inference
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 01 2020
21 01 2020
Historique:
received:
11
03
2019
revised:
25
06
2019
accepted:
13
12
2019
entrez:
23
1
2020
pubmed:
23
1
2020
medline:
18
3
2021
Statut:
ppublish
Résumé
Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.
Identifiants
pubmed: 31968263
pii: S2211-1247(19)31711-5
doi: 10.1016/j.celrep.2019.12.054
pmc: PMC7039998
mid: NIHMS1551577
pii:
doi:
Substances chimiques
Chromatin
0
Interferon Type I
0
Retinoic Acid Receptor alpha
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
914-931.e9Subventions
Organisme : NIAID NIH HHS
ID : R21 AI084633
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI032972
Pays : United States
Organisme : NIAID NIH HHS
ID : F32 AI093231
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI100627
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI025032
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150464
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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