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

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dc.contributor.author Cebrià i Costa, Joan Pau, 1989-
dc.contributor.author Pascual-Reguant, Laura
dc.contributor.author Gonzalez-Perez, Abel
dc.contributor.author Serra Bardenys, Gemma, 1992-
dc.contributor.author Querol, J.
dc.contributor.author Cosín, M.
dc.contributor.author Verde, Gaetano
dc.contributor.author Cigliano, Riccardo Aiese
dc.contributor.author Sanseverino, Walter
dc.contributor.author Segura-Bayona, Sandra
dc.contributor.author Iturbide Martínez de Albéniz, Ane, 1989-
dc.contributor.author Andreu Martínez, David
dc.contributor.author Nuciforo, Paolo G.
dc.contributor.author Bernado-Morales, C.
dc.contributor.author Rodilla, Verónica
dc.contributor.author Arribas, Joaquín
dc.contributor.author Yélamos López, José
dc.contributor.author García de Herreros, Antonio
dc.contributor.author Stracker, Travis
dc.contributor.author Peiró Sales, Sandra
dc.date.accessioned 2020-03-24T07:31:25Z
dc.date.available 2020-03-24T07:31:25Z
dc.date.issued 2020
dc.identifier.citation Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, et al. LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells. Oncogene. 2020 Jan; 39(1):79-121. DOI: 10.1038/s41388-019-0969-1
dc.identifier.issn 0950-9232
dc.identifier.uri http://hdl.handle.net/10230/44004
dc.description.abstract 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.
dc.description.sponsorship 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Oncogene. 2020 Jan;39(1):79-121
dc.rights This 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/
dc.rights.uri http://creativecommons.org/licenses/by/4.0
dc.subject.other Mama -- Càncer -- Aspectes genètics
dc.subject.other Mama -- Càncer -- Tractament
dc.title LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41388-019-0969-1
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68354
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/AGL2014-52395-C2-2-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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