The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response

A precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the mole...

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Autores: Asensio Juan, Elena, Fueyo, Raquel, Pappa, Stella, Iacobucci, Simona, Badosa, Carmen, Lois Olmo, Sergio, Balada, Miriam, Bosch Presegué, Laia, Vaquero García, Alejandro, Gutiérrez, Sara, Caelles Franch, Carme, Gallego González, Carmen, Cruz, Xavier de la, Martínez Balbás, Marian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/123683
Acceso en línea:https://hdl.handle.net/2445/123683
Access Level:acceso abierto
Palabra clave:Interferó
Histones
Proteïnes
Interferon
Proteins
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spelling The histone demethylase PHF8 is a molecular safeguard of the IFNgamma responseAsensio Juan, ElenaFueyo, RaquelPappa, StellaIacobucci, SimonaBadosa, CarmenLois Olmo, SergioBalada, MiriamBosch Presegué, LaiaVaquero García, AlejandroGutiérrez, SaraCaelles Franch, CarmeGallego González, CarmenCruz, Xavier de laMartínez Balbás, MarianInterferóHistonesProteïnesInterferonHistonesProteinsA precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the molecular mechanisms preventing non-specific activation and allowing a quick response upon signal activation are not yet fully understood. In this paper we uncover a new function of PHF8 blocking signal independent activation of immune gene promoters. Affinity purifications coupled with mass spectrometry analysis identified SIN3A and HDAC1 corepressors as new PHF8 interacting partners. Further molecular analysis demonstrated that prior to interferon gamma (IFNγ) stimulation, PHF8 is bound to a subset of IFNγ-responsive promoters. Through the association with HDAC1 and SIN3A, PHF8 keeps the promoters in a silent state, maintaining low levels of H4K20me1. Upon IFNγ treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, correlating with an increase in H4K20me1 and transcriptional activation. Our data strongly indicate that in addition to its well-characterized function as a coactivator, PHF8 safeguards transcription to allow an accurate immune response.Oxford University Press2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/123683Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1093/nar/gkw1346Nucleic Acids Research, 2017, vol. 45, num. 7, p. 3800-3811https://doi.org/10.1093/nar/gkw1346cc-by-nc (c) Asensio-Juan, E. et al., 2017http://creativecommons.org/licenses/by-nc/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1236832026-05-29T05:05:01Z
dc.title.none.fl_str_mv The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
title The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
spellingShingle The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
Asensio Juan, Elena
Interferó
Histones
Proteïnes
Interferon
Histones
Proteins
title_short The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
title_full The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
title_fullStr The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
title_full_unstemmed The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
title_sort The histone demethylase PHF8 is a molecular safeguard of the IFNgamma response
dc.creator.none.fl_str_mv Asensio Juan, Elena
Fueyo, Raquel
Pappa, Stella
Iacobucci, Simona
Badosa, Carmen
Lois Olmo, Sergio
Balada, Miriam
Bosch Presegué, Laia
Vaquero García, Alejandro
Gutiérrez, Sara
Caelles Franch, Carme
Gallego González, Carmen
Cruz, Xavier de la
Martínez Balbás, Marian
author Asensio Juan, Elena
author_facet Asensio Juan, Elena
Fueyo, Raquel
Pappa, Stella
Iacobucci, Simona
Badosa, Carmen
Lois Olmo, Sergio
Balada, Miriam
Bosch Presegué, Laia
Vaquero García, Alejandro
Gutiérrez, Sara
Caelles Franch, Carme
Gallego González, Carmen
Cruz, Xavier de la
Martínez Balbás, Marian
author_role author
author2 Fueyo, Raquel
Pappa, Stella
Iacobucci, Simona
Badosa, Carmen
Lois Olmo, Sergio
Balada, Miriam
Bosch Presegué, Laia
Vaquero García, Alejandro
Gutiérrez, Sara
Caelles Franch, Carme
Gallego González, Carmen
Cruz, Xavier de la
Martínez Balbás, Marian
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Interferó
Histones
Proteïnes
Interferon
Histones
Proteins
topic Interferó
Histones
Proteïnes
Interferon
Histones
Proteins
description A precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the molecular mechanisms preventing non-specific activation and allowing a quick response upon signal activation are not yet fully understood. In this paper we uncover a new function of PHF8 blocking signal independent activation of immune gene promoters. Affinity purifications coupled with mass spectrometry analysis identified SIN3A and HDAC1 corepressors as new PHF8 interacting partners. Further molecular analysis demonstrated that prior to interferon gamma (IFNγ) stimulation, PHF8 is bound to a subset of IFNγ-responsive promoters. Through the association with HDAC1 and SIN3A, PHF8 keeps the promoters in a silent state, maintaining low levels of H4K20me1. Upon IFNγ treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, correlating with an increase in H4K20me1 and transcriptional activation. Our data strongly indicate that in addition to its well-characterized function as a coactivator, PHF8 safeguards transcription to allow an accurate immune response.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/123683
url https://hdl.handle.net/2445/123683
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/nar/gkw1346
Nucleic Acids Research, 2017, vol. 45, num. 7, p. 3800-3811
https://doi.org/10.1093/nar/gkw1346
dc.rights.none.fl_str_mv cc-by-nc (c) Asensio-Juan, E. et al., 2017
http://creativecommons.org/licenses/by-nc/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc (c) Asensio-Juan, E. et al., 2017
http://creativecommons.org/licenses/by-nc/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
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 Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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