The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621223
Title:
The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells.
Authors:
Poppe, Michael; Wittig, Sascha; Jurida, Liane; Bartkuhn, Marek; Wilhelm, Jochen; Müller, Helmut; Beuerlein, Knut; Karl, Nadja; Bhuju, Sabin; Ziebuhr, John; Schmitz, M Lienhard; Kracht, Michael
Abstract:
Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells. 2017, 13 (3):e1006286 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Mar-2017
URI:
http://hdl.handle.net/10033/621223
DOI:
10.1371/journal.ppat.1006286
PubMed ID:
28355270
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorPoppe, Michaelen
dc.contributor.authorWittig, Saschaen
dc.contributor.authorJurida, Lianeen
dc.contributor.authorBartkuhn, Mareken
dc.contributor.authorWilhelm, Jochenen
dc.contributor.authorMüller, Helmuten
dc.contributor.authorBeuerlein, Knuten
dc.contributor.authorKarl, Nadjaen
dc.contributor.authorBhuju, Sabinen
dc.contributor.authorZiebuhr, Johnen
dc.contributor.authorSchmitz, M Lienharden
dc.contributor.authorKracht, Michaelen
dc.date.accessioned2018-01-04T09:46:44Z-
dc.date.available2018-01-04T09:46:44Z-
dc.date.issued2017-03-
dc.identifier.citationThe NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells. 2017, 13 (3):e1006286 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid28355270-
dc.identifier.doi10.1371/journal.ppat.1006286-
dc.identifier.urihttp://hdl.handle.net/10033/621223-
dc.description.abstractCoronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshCell Lineen
dc.subject.meshChromatinen
dc.subject.meshChromatin Immunoprecipitationen
dc.subject.meshCoronavirus 229E, Humanen
dc.subject.meshCoronavirus Infectionsen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHumansen
dc.subject.meshImmunoblottingen
dc.subject.meshLaser Capture Microdissectionen
dc.subject.meshMicroscopy, Fluorescenceen
dc.subject.meshNF-kappa Ben
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshTranscriptomeen
dc.titleThe NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalPLoS pathogensen

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