Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats

Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs...

ver descrição completa

Detalhes bibliográficos
Autores: Izquierdo Bouldstridge, Andrea, Bustillos, Alberto, Bonet-Costa, Carles, Aribau-Miralbés, Patricia, García-Gomis, Daniel, Dabad, Marc, Esteve-Codina, Anna, Pascual-Reguant, Laura, 1990-, Peiró Sales, Sandra, Esteller, Manel, Murtha, Matthew, Millán Ariño, Lluís, 1984-, Jordan Vallès, Albert
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos: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:10230/58841
Acesso em linha:http://hdl.handle.net/10230/58841
http://dx.doi.org/10.1093/nar/gkx746
Access Level:acceso abierto
Palavra-chave:Histones
Mama -- Càncer
Cromatina
id ES_e71096f2e2fba80c71af2355004eb59c
oai_identifier_str oai:recercat.cat:10230/58841
network_acronym_str ES
network_name_str España
repository_id_str
spelling Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeatsIzquierdo Bouldstridge, AndreaBustillos, AlbertoBonet-Costa, CarlesAribau-Miralbés, PatriciaGarcía-Gomis, DanielDabad, MarcEsteve-Codina, AnnaPascual-Reguant, Laura, 1990-Peiró Sales, SandraEsteller, ManelMurtha, MatthewMillán Ariño, Lluís, 1984-Jordan Vallès, AlbertHistonesMama -- CàncerCromatinaHistone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response.Spanish Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund [BFU2014–52237-P]. A.B. received a predoctoral fellowship from SENESCYT from Ecuador. M.D. was recipient of a fellowship from MINECO [PTA2014–09515-I]. A.E.-C. was funded by the RED-BIO project of the Spanish National Bioinformatics Institute (INB) [PT13/0001/0044]. The INB is funded by the Spanish National Health Institute Carlos III (ISCIII) and MINECO. Funding for open access charge: Spanish Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund [BFU2014-52237-P].Oxford University Press202420242017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/58841http://dx.doi.org/10.1093/nar/gkx746reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNucleic Acids Research. 2017 Nov 16;45(20):11622-42info:eu-repo/grantAgreement/ES/1PE/BFU2014–52237-Pinfo:eu-repo/grantAgreement/ES/1PE/BFU2014-52237-P© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/588412026-05-29T05:05:01Z
dc.title.none.fl_str_mv Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
title Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
spellingShingle Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
Izquierdo Bouldstridge, Andrea
Histones
Mama -- Càncer
Cromatina
title_short Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
title_full Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
title_fullStr Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
title_full_unstemmed Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
title_sort Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats
dc.creator.none.fl_str_mv Izquierdo Bouldstridge, Andrea
Bustillos, Alberto
Bonet-Costa, Carles
Aribau-Miralbés, Patricia
García-Gomis, Daniel
Dabad, Marc
Esteve-Codina, Anna
Pascual-Reguant, Laura, 1990-
Peiró Sales, Sandra
Esteller, Manel
Murtha, Matthew
Millán Ariño, Lluís, 1984-
Jordan Vallès, Albert
author Izquierdo Bouldstridge, Andrea
author_facet Izquierdo Bouldstridge, Andrea
Bustillos, Alberto
Bonet-Costa, Carles
Aribau-Miralbés, Patricia
García-Gomis, Daniel
Dabad, Marc
Esteve-Codina, Anna
Pascual-Reguant, Laura, 1990-
Peiró Sales, Sandra
Esteller, Manel
Murtha, Matthew
Millán Ariño, Lluís, 1984-
Jordan Vallès, Albert
author_role author
author2 Bustillos, Alberto
Bonet-Costa, Carles
Aribau-Miralbés, Patricia
García-Gomis, Daniel
Dabad, Marc
Esteve-Codina, Anna
Pascual-Reguant, Laura, 1990-
Peiró Sales, Sandra
Esteller, Manel
Murtha, Matthew
Millán Ariño, Lluís, 1984-
Jordan Vallès, Albert
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Histones
Mama -- Càncer
Cromatina
topic Histones
Mama -- Càncer
Cromatina
description Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response.
publishDate 2017
dc.date.none.fl_str_mv 2017
2024
2024
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 http://hdl.handle.net/10230/58841
http://dx.doi.org/10.1093/nar/gkx746
url http://hdl.handle.net/10230/58841
http://dx.doi.org/10.1093/nar/gkx746
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nucleic Acids Research. 2017 Nov 16;45(20):11622-42
info:eu-repo/grantAgreement/ES/1PE/BFU2014–52237-P
info:eu-repo/grantAgreement/ES/1PE/BFU2014-52237-P
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
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: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
_version_ 1869422821748244480
score 15,811543

Registos relacionados