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 Tomàs, Marta
  • 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.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.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.doi http://dx.doi.org/10.1038/s41388-019-0969-1
  • dc.identifier.issn 0950-9232
  • dc.identifier.uri http://hdl.handle.net/10230/44004
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Oncogene. 2020 Jan;39(1):79-121
  • 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 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.accessRights info:eu-repo/semantics/openAccess
  • 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.type.version info:eu-repo/semantics/publishedVersion

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