Cebrià i Costa, Joan Pau, 1989-Pascual-Reguant, LauraGonzalez-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, Sandra2020-03-242020-03-242020Cebrià-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/s41388-019-0969-10950-9232http://hdl.handle.net/10230/44004Oxidation 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.application/pdfengThis 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/Mama -- Càncer -- Aspectes genèticsMama -- Càncer -- Tractamentinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41388-019-0969-1info:eu-repo/semantics/openAccess