dc.contributor.author | Patil, Vibha | |
dc.contributor.author | Cuenin, Cyrille | |
dc.contributor.author | Chung, Felicia | |
dc.contributor.author | Rodríguez Aguilera, Jesús R. | |
dc.contributor.author | Fernández Jiménez, Nora | |
dc.contributor.author | Romero Garmendia, Irati | |
dc.contributor.author | Bilbao Catalá, José Ramón | |
dc.contributor.author | Cahais, Vincent | |
dc.contributor.author | Rothwell, Joseph | |
dc.contributor.author | Herceg, Zdenko | |
dc.date.accessioned | 2020-01-31T08:52:39Z | |
dc.date.available | 2020-01-31T08:52:39Z | |
dc.date.issued | 2019-09-06 | |
dc.identifier.citation | Nucleic Acids Research 47(19) : 10072-10085 (2019) | es_ES |
dc.identifier.issn | 0305-1048 | |
dc.identifier.issn | 1362-4962 | |
dc.identifier.uri | http://hdl.handle.net/10810/39747 | |
dc.description.abstract | Mitochondrial dysfunction plays critical roles in cancer development and related therapeutic response; however, exact molecular mechanisms remain unclear. Recently, alongside the discovery of mitochondrial-specific DNA methyltransferases, global and site-specific methylation of the mitochondrial genome has been described. Investigation of any functional consequences however remains unclear and debated due to insufficient evidence of the quantitative degree and frequency of mitochondrial DNA (mtDNA) methylation. This study uses WGBS to provide the first quantitative report of mtDNA methylation at single base pair resolution. The data show that mitochondrial genomes are extensively methylated predominantly at non-CpG sites. Importantly, these methylation patterns display notable differences between normal and cancer cells. Furthermore, knockdown of DNA methyltransferase enzymes resulted in a marked global reduction of mtDNA methylation levels, indicating these enzymes may be associated with the establishment and/or maintenance of mtDNA methylation. DNMT3B knockdown cells displayed a comparatively pronounced global reduction in mtDNA methylation with concomitant increases in gene expression, suggesting a potential functional link between methylation and gene expression. Together these results demonstrate reproducible, non-random methylation patterns of mtDNA and challenge the notion that mtDNA is lowly methylated. This study discusses key differences in methodology that suggest future investigations must allow for techniques that assess both CpG and non-CpG methylation. | es_ES |
dc.description.sponsorship | Institut National du Cancer (INCa, France); European Commission (EC) Seventh Framework Programme (FP7) Translational Cancer Research (TRANSCAN) Framework; Foundation ARC pour la Recherche sur le Cancer (France); Plan Cancer-Eva-Inserm research grant (to Z.H.); Postdoctoral Fellowship from International Agency for Research on Cancer (to V.P.), partially supported by the EC FP7 Marie Curie Actions -People -Co-funding of regional, national and international programmes (COFUND)'. Funding for open access charge: Institut National du Cancer (INCa, France); European Commission (EC) Seventh Framework Programme (FP7) Translational Cancer Research (TRANSCAN) Framework; Foundation ARC pour la Recherche sur le Cancer (France); Plan Cancer-Eva-Inserm research grant (to Z.H.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | displacement loop | es_ES |
dc.subject | expression | es_ES |
dc.subject | replication | es_ES |
dc.subject | promoter | es_ES |
dc.subject | origin | es_ES |
dc.subject | number | es_ES |
dc.subject | region | es_ES |
dc.subject | cells | es_ES |
dc.subject | shows | es_ES |
dc.subject | mtdna | es_ES |
dc.title | Human mitochondrial DNA is extensively methylated in a non-CpG context | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is available under the Creative Commons CC-BY-NC license and permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://academic.oup.com/nar/article/47/19/10072/5563943#165683721 | es_ES |
dc.identifier.doi | 10.1093/nar/gkz762 | |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |