Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis

Autores
Trilling, Mirko; Bellora, Nicolás; Rutkowski, Andrzej J.; de Graaf, Miranda; Dickinson, Paul; Robertson, Kevin; Da Costa, Olivia Prazeres; Ghazal, Peter; Friedel, Caroline C.; Albà, M. Mar; Dölken, Lars
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Interferons (IFN) play a pivotal role in innate immunity, orchestrating a cell-intrinsic anti-pathogenic state and stimulating adaptive immune responses. The complex interplay between the primary response to IFNs and its modulation by positive and negative feedback loops is incompletely understood. Here, we implement the combination of high-resolution gene-expression profiling of nascent RNA with translational inhibition of secondary feedback by cycloheximide. Unexpectedly, this approach revealed a prominent role of negative feedback mechanisms during the immediate (≤60 min) IFNα response. In contrast, a more complex picture involving both negative and positive feedback loops was observed on IFNγ treatment. IFNγ-induced repression of genes associated with regulation of gene expression, cellular development, apoptosis and cell growth resulted from cycloheximide-resistant primary IFNγ signalling. In silico promoter analysis revealed significant overrepresentation of SP1/SP3-binding sites and/or GC-rich stretches. Although signal transducer and activator of transcription 1 (STAT1)-binding sites were not overrepresented, repression was lost in absence of STAT1. Interestingly, basal expression of the majority of these IFNγ-repressed genes was dependent on STAT1 in IFN-naïve fibroblasts. Finally, IFNγ-mediated repression was also found to be evident in primary murine macrophages. IFN-repressed genes include negative regulators of innate and stress response, and their decrease may thus aid the establishment of a signalling perceptive milieu.
Fil: Trilling, Mirko. Universitat Duisburg - Essen; Alemania
Fil: Bellora, Nicolás. Parque de Investigación Biomédica de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina
Fil: Rutkowski, Andrzej J.. University of Cambridge; Reino Unido
Fil: de Graaf, Miranda. University of Cambridge; Reino Unido
Fil: Dickinson, Paul. University Of Edinburgh; Reino Unido
Fil: Robertson, Kevin. University Of Edinburgh; Reino Unido
Fil: Da Costa, Olivia Prazeres. Universitat Technical Zu Munich; Alemania
Fil: Ghazal, Peter. University Of Edinburgh; Reino Unido
Fil: Friedel, Caroline C.. Ludwig-Maximilians-University Munich; Alemania
Fil: Albà, M. Mar. Institució Catalana de Recerca I Estudis Avancats; España. Parque de Investigación Biomédica de Barcelona; España
Fil: Dölken, Lars. University of Cambridge; Reino Unido
Materia
interferon
4sU-tagging
bioinformatics
expression
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6809
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6809
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysisTrilling, MirkoBellora, NicolásRutkowski, Andrzej J.de Graaf, MirandaDickinson, PaulRobertson, KevinDa Costa, Olivia PrazeresGhazal, PeterFriedel, Caroline C.Albà, M. MarDölken, Larsinterferon4sU-taggingbioinformaticsexpressionhttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Interferons (IFN) play a pivotal role in innate immunity, orchestrating a cell-intrinsic anti-pathogenic state and stimulating adaptive immune responses. The complex interplay between the primary response to IFNs and its modulation by positive and negative feedback loops is incompletely understood. Here, we implement the combination of high-resolution gene-expression profiling of nascent RNA with translational inhibition of secondary feedback by cycloheximide. Unexpectedly, this approach revealed a prominent role of negative feedback mechanisms during the immediate (≤60 min) IFNα response. In contrast, a more complex picture involving both negative and positive feedback loops was observed on IFNγ treatment. IFNγ-induced repression of genes associated with regulation of gene expression, cellular development, apoptosis and cell growth resulted from cycloheximide-resistant primary IFNγ signalling. In silico promoter analysis revealed significant overrepresentation of SP1/SP3-binding sites and/or GC-rich stretches. Although signal transducer and activator of transcription 1 (STAT1)-binding sites were not overrepresented, repression was lost in absence of STAT1. Interestingly, basal expression of the majority of these IFNγ-repressed genes was dependent on STAT1 in IFN-naïve fibroblasts. Finally, IFNγ-mediated repression was also found to be evident in primary murine macrophages. IFN-repressed genes include negative regulators of innate and stress response, and their decrease may thus aid the establishment of a signalling perceptive milieu.Fil: Trilling, Mirko. Universitat Duisburg - Essen; AlemaniaFil: Bellora, Nicolás. Parque de Investigación Biomédica de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; ArgentinaFil: Rutkowski, Andrzej J.. University of Cambridge; Reino UnidoFil: de Graaf, Miranda. University of Cambridge; Reino UnidoFil: Dickinson, Paul. University Of Edinburgh; Reino UnidoFil: Robertson, Kevin. University Of Edinburgh; Reino UnidoFil: Da Costa, Olivia Prazeres. Universitat Technical Zu Munich; AlemaniaFil: Ghazal, Peter. University Of Edinburgh; Reino UnidoFil: Friedel, Caroline C.. Ludwig-Maximilians-University Munich; AlemaniaFil: Albà, M. Mar. Institució Catalana de Recerca I Estudis Avancats; España. Parque de Investigación Biomédica de Barcelona; EspañaFil: Dölken, Lars. University of Cambridge; Reino UnidoOxford University Press2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6809Trilling, Mirko; Bellora, Nicolás; Rutkowski, Andrzej J.; de Graaf, Miranda; Dickinson, Paul; et al.; Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis; Oxford University Press; Nucleic Acids Research; 41; 17; 9-2013; 8107-81250305-10481362-4962enginfo:eu-repo/semantics/altIdentifier/url/http://nar.oxfordjournals.org/content/41/17/8107info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783172/info:eu-repo/semantics/altIdentifier/pmid/PMC3783172info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkt589info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:27Zoai:ri.conicet.gov.ar:11336/6809instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:39:27.333CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
title Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
spellingShingle Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
Trilling, Mirko
interferon
4sU-tagging
bioinformatics
expression
title_short Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
title_full Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
title_fullStr Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
title_full_unstemmed Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
title_sort Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis
dc.creator.none.fl_str_mv Trilling, Mirko
Bellora, Nicolás
Rutkowski, Andrzej J.
de Graaf, Miranda
Dickinson, Paul
Robertson, Kevin
Da Costa, Olivia Prazeres
Ghazal, Peter
Friedel, Caroline C.
Albà, M. Mar
Dölken, Lars
author Trilling, Mirko
author_facet Trilling, Mirko
Bellora, Nicolás
Rutkowski, Andrzej J.
de Graaf, Miranda
Dickinson, Paul
Robertson, Kevin
Da Costa, Olivia Prazeres
Ghazal, Peter
Friedel, Caroline C.
Albà, M. Mar
Dölken, Lars
author_role author
author2 Bellora, Nicolás
Rutkowski, Andrzej J.
de Graaf, Miranda
Dickinson, Paul
Robertson, Kevin
Da Costa, Olivia Prazeres
Ghazal, Peter
Friedel, Caroline C.
Albà, M. Mar
Dölken, Lars
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv interferon
4sU-tagging
bioinformatics
expression
topic interferon
4sU-tagging
bioinformatics
expression
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Interferons (IFN) play a pivotal role in innate immunity, orchestrating a cell-intrinsic anti-pathogenic state and stimulating adaptive immune responses. The complex interplay between the primary response to IFNs and its modulation by positive and negative feedback loops is incompletely understood. Here, we implement the combination of high-resolution gene-expression profiling of nascent RNA with translational inhibition of secondary feedback by cycloheximide. Unexpectedly, this approach revealed a prominent role of negative feedback mechanisms during the immediate (≤60 min) IFNα response. In contrast, a more complex picture involving both negative and positive feedback loops was observed on IFNγ treatment. IFNγ-induced repression of genes associated with regulation of gene expression, cellular development, apoptosis and cell growth resulted from cycloheximide-resistant primary IFNγ signalling. In silico promoter analysis revealed significant overrepresentation of SP1/SP3-binding sites and/or GC-rich stretches. Although signal transducer and activator of transcription 1 (STAT1)-binding sites were not overrepresented, repression was lost in absence of STAT1. Interestingly, basal expression of the majority of these IFNγ-repressed genes was dependent on STAT1 in IFN-naïve fibroblasts. Finally, IFNγ-mediated repression was also found to be evident in primary murine macrophages. IFN-repressed genes include negative regulators of innate and stress response, and their decrease may thus aid the establishment of a signalling perceptive milieu.
Fil: Trilling, Mirko. Universitat Duisburg - Essen; Alemania
Fil: Bellora, Nicolás. Parque de Investigación Biomédica de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina
Fil: Rutkowski, Andrzej J.. University of Cambridge; Reino Unido
Fil: de Graaf, Miranda. University of Cambridge; Reino Unido
Fil: Dickinson, Paul. University Of Edinburgh; Reino Unido
Fil: Robertson, Kevin. University Of Edinburgh; Reino Unido
Fil: Da Costa, Olivia Prazeres. Universitat Technical Zu Munich; Alemania
Fil: Ghazal, Peter. University Of Edinburgh; Reino Unido
Fil: Friedel, Caroline C.. Ludwig-Maximilians-University Munich; Alemania
Fil: Albà, M. Mar. Institució Catalana de Recerca I Estudis Avancats; España. Parque de Investigación Biomédica de Barcelona; España
Fil: Dölken, Lars. University of Cambridge; Reino Unido
description Interferons (IFN) play a pivotal role in innate immunity, orchestrating a cell-intrinsic anti-pathogenic state and stimulating adaptive immune responses. The complex interplay between the primary response to IFNs and its modulation by positive and negative feedback loops is incompletely understood. Here, we implement the combination of high-resolution gene-expression profiling of nascent RNA with translational inhibition of secondary feedback by cycloheximide. Unexpectedly, this approach revealed a prominent role of negative feedback mechanisms during the immediate (≤60 min) IFNα response. In contrast, a more complex picture involving both negative and positive feedback loops was observed on IFNγ treatment. IFNγ-induced repression of genes associated with regulation of gene expression, cellular development, apoptosis and cell growth resulted from cycloheximide-resistant primary IFNγ signalling. In silico promoter analysis revealed significant overrepresentation of SP1/SP3-binding sites and/or GC-rich stretches. Although signal transducer and activator of transcription 1 (STAT1)-binding sites were not overrepresented, repression was lost in absence of STAT1. Interestingly, basal expression of the majority of these IFNγ-repressed genes was dependent on STAT1 in IFN-naïve fibroblasts. Finally, IFNγ-mediated repression was also found to be evident in primary murine macrophages. IFN-repressed genes include negative regulators of innate and stress response, and their decrease may thus aid the establishment of a signalling perceptive milieu.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/6809
Trilling, Mirko; Bellora, Nicolás; Rutkowski, Andrzej J.; de Graaf, Miranda; Dickinson, Paul; et al.; Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis; Oxford University Press; Nucleic Acids Research; 41; 17; 9-2013; 8107-8125
0305-1048
1362-4962
url http://hdl.handle.net/11336/6809
identifier_str_mv Trilling, Mirko; Bellora, Nicolás; Rutkowski, Andrzej J.; de Graaf, Miranda; Dickinson, Paul; et al.; Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis; Oxford University Press; Nucleic Acids Research; 41; 17; 9-2013; 8107-8125
0305-1048
1362-4962
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://nar.oxfordjournals.org/content/41/17/8107
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783172/
info:eu-repo/semantics/altIdentifier/pmid/PMC3783172
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkt589
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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