LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

Cebrià i Costa, Joan Pau, 1989-; Pascual-Reguant, Laura, 1990-; Gonzalez-Perez, Abel; Serra Bardenys, Gemma, 1992-; Querol, J.; Cosín Tomàs, Marta; Verde, Gaetano; Cigliano, Riccardo Aiese; Sanseverino, Walter; Segura-Bayona, Sandra; Iturbide Martínez de Albéniz, Ane, 1989-; Andreu Martínez, David; Nuciforo, Paolo G.; Bernado-Morales, C.; Rodilla, Verónica; Arribas, Joaquín; Yélamos López, José; García de Herreros, Antonio; Stracker, Travis; Peiró Sales, Sandra

LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast can...

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Detalles Bibliográficos
Autores:	Cebrià i Costa, Joan Pau, 1989-, Pascual-Reguant, Laura, 1990-, Gonzalez-Perez, Abel, Serra Bardenys, Gemma, 1992-, Querol, J., Cosín Tomàs, Marta, Verde, Gaetano, Cigliano, Riccardo Aiese, Sanseverino, Walter, Segura-Bayona, Sandra, Iturbide Martínez de Albéniz, Ane, 1989-, Andreu Martínez, David, Nuciforo, Paolo G., Bernado-Morales, C., Rodilla, Verónica, Arribas, Joaquín, Yélamos López, José, García de Herreros, Antonio, Stracker, Travis, Peiró Sales, Sandra
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2020
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:10230/44004
Acceso en línea:	http://hdl.handle.net/10230/44004 http://dx.doi.org/10.1038/s41388-019-0969-1
Access Level:	acceso abierto
Palabra clave:	Mama -- Càncer -- Aspectes genètics Mama -- Càncer -- Tractament

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spelling	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cellsCebrià i Costa, Joan Pau, 1989-Pascual-Reguant, Laura, 1990-Gonzalez-Perez, AbelSerra Bardenys, Gemma, 1992-Querol, J.Cosín Tomàs, MartaVerde, GaetanoCigliano, Riccardo AieseSanseverino, WalterSegura-Bayona, SandraIturbide Martínez de Albéniz, Ane, 1989-Andreu Martínez, DavidNuciforo, Paolo G.Bernado-Morales, C.Rodilla, VerónicaArribas, JoaquínYélamos López, JoséGarcía de Herreros, AntonioStracker, TravisPeiró Sales, SandraMama -- Càncer -- Aspectes genèticsMama -- Càncer -- TractamentOxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI12/01250; CP08/00223; PI16/00253; and CB16/12/00449), MINECO (SAF2013-48849-C2-1-R) to SP, BFU2015-68354 to THS, Breast Cancer Research Foundation (BCRF-17-008) to JA, AGL2014-52395-C2-2-R to DA, Worldwide Cancer Research, Red Temática de Investigación Cooperativa en Cáncer (RD012/0036/005), Fundación Científica de la Asociación Española contra el Cáncer, and Fundació La Marató TV3.THS was supported by institutional funding (MINECO) through theCentres of Excellence Severo Ochoa award and the CERCA Pro-gramme of the Catalan Government, and SS-B, by a Fundació LaCaixa fellowship. We thank La Caixa Foundation and Cellex Foun-dation for provide research facilities and equipment. GV has received f unding from the MINECO (a “Juan de la Cierva Incorporation ” fellowship; IJCI-2014-20723). SP was a recipient of a Miguel Servet contract (ISCIII/FIS), and AI, JPC-C, LP-G, and GS-B are supported by contracts from Worldwide Cancer Research, Fundació La MaratóTV3, Fundació FERO, and a FI Fellowship from the Generalitat de Catalunya, respectively.Nature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44004http://dx.doi.org/10.1038/s41388-019-0969-1reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésOncogene. 2020 Jan;39(1):79-121info:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-1-Rinfo:eu-repo/grantAgreement/ES/1PE/BFU2015-68354info:eu-repo/grantAgreement/ES/1PE/AGL2014-52395-C2-2-RThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intendeduse is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10230/440042026-05-29T05:05:01Z
dc.title.none.fl_str_mv	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
title	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
spellingShingle	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells Cebrià i Costa, Joan Pau, 1989- Mama -- Càncer -- Aspectes genètics Mama -- Càncer -- Tractament
title_short	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
title_full	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
title_fullStr	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
title_full_unstemmed	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
title_sort	LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
dc.creator.none.fl_str_mv	Cebrià i Costa, Joan Pau, 1989- Pascual-Reguant, Laura, 1990- Gonzalez-Perez, Abel Serra Bardenys, Gemma, 1992- Querol, J. Cosín Tomàs, Marta Verde, Gaetano Cigliano, Riccardo Aiese Sanseverino, Walter Segura-Bayona, Sandra Iturbide Martínez de Albéniz, Ane, 1989- Andreu Martínez, David Nuciforo, Paolo G. Bernado-Morales, C. Rodilla, Verónica Arribas, Joaquín Yélamos López, José García de Herreros, Antonio Stracker, Travis Peiró Sales, Sandra
author	Cebrià i Costa, Joan Pau, 1989-
author_facet	Cebrià i Costa, Joan Pau, 1989- Pascual-Reguant, Laura, 1990- Gonzalez-Perez, Abel Serra Bardenys, Gemma, 1992- Querol, J. Cosín Tomàs, Marta Verde, Gaetano Cigliano, Riccardo Aiese Sanseverino, Walter Segura-Bayona, Sandra Iturbide Martínez de Albéniz, Ane, 1989- Andreu Martínez, David Nuciforo, Paolo G. Bernado-Morales, C. Rodilla, Verónica Arribas, Joaquín Yélamos López, José García de Herreros, Antonio Stracker, Travis Peiró Sales, Sandra
author_role	author
author2	Pascual-Reguant, Laura, 1990- Gonzalez-Perez, Abel Serra Bardenys, Gemma, 1992- Querol, J. Cosín Tomàs, Marta Verde, Gaetano Cigliano, Riccardo Aiese Sanseverino, Walter Segura-Bayona, Sandra Iturbide Martínez de Albéniz, Ane, 1989- Andreu Martínez, David Nuciforo, Paolo G. Bernado-Morales, C. Rodilla, Verónica Arribas, Joaquín Yélamos López, José García de Herreros, Antonio Stracker, Travis Peiró Sales, Sandra
author2_role	author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Mama -- Càncer -- Aspectes genètics Mama -- Càncer -- Tractament
topic	Mama -- Càncer -- Aspectes genètics Mama -- Càncer -- Tractament
description	Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.
publishDate	2020
dc.date.none.fl_str_mv	2020 2020 2020
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/10230/44004 http://dx.doi.org/10.1038/s41388-019-0969-1
url	http://hdl.handle.net/10230/44004 http://dx.doi.org/10.1038/s41388-019-0969-1
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Oncogene. 2020 Jan;39(1):79-121 info:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-1-R info:eu-repo/grantAgreement/ES/1PE/BFU2015-68354 info:eu-repo/grantAgreement/ES/1PE/AGL2014-52395-C2-2-R
dc.rights.none.fl_str_mv	http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Nature Research
publisher.none.fl_str_mv	Nature Research
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)
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LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

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