Impact of DNA methylation on 3D genome structure

Buitrago, Diana; Labrador, Mireia; Arcon, Juan Pablo; Lema, Rafael; Flores, Oscar; Esteve-Codina, Anna; Blanc, Julie; Villegas, Núria; Bellido, David; Gut, Marta; Dans, Pablo D.; Heath, Simon; Gut, Ivo Glynne; Brun-Heath, Isabelle; Orozco, Modesto

Impact of DNA methylation on 3D genome structure

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dc.contributor.author Buitrago, Diana
dc.contributor.author Labrador, Mireia
dc.contributor.author Arcon, Juan Pablo
dc.contributor.author Lema, Rafael
dc.contributor.author Flores, Oscar
dc.contributor.author Esteve-Codina, Anna
dc.contributor.author Blanc, Julie
dc.contributor.author Villegas, Núria
dc.contributor.author Bellido, David
dc.contributor.author Gut, Marta
dc.contributor.author Dans, Pablo D.
dc.contributor.author Heath, Simon
dc.contributor.author Gut, Ivo Glynne
dc.contributor.author Brun-Heath, Isabelle
dc.contributor.author Orozco, Modesto
dc.date.accessioned 2021-11-26T06:48:52Z
dc.date.available 2021-11-26T06:48:52Z
dc.date.issued 2021
dc.description.abstract Determining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5' end of the gene increasing gradually toward the 3' end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.
dc.description.sponsorship This work has been supported by the Spanish Ministry of Science (BIO2012-32868), the Catalan SGR, the Instituto Nacional de Bioinformática, the European Research Council (ERC_SimDNA) and the BioExcel and MuG VRE H2000 projects. M.O. is an ICREA Academia Fellow. This project also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754510 [to J.P.A. and M.O.]. The work of S.H. was supported by the Spanish Ministry of Science (PGC2018-099640-B-I00). A.E.C. is funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER.
dc.format.mimetype application/pdf
dc.identifier.citation Buitrago D, Labrador M, Arcon JP, Lema R, Flores O, Esteve-Codina A, Blanc J, Villegas N, Bellido D, Gut M, Dans PD, Heath SC, Gut IG, Brun Heath I, Orozco M. Impact of DNA methylation on 3D genome structure. Nat Commun. 2021;12(1):3243. DOI: 10.1038/s41467-021-23142-8
dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-23142-8
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/49064
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2021;12(1):3243
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754510
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099640-B-I00
dc.rights © The Author(s) 2021. Open Access 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 intended use 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.keyword Chromatin remodelling
dc.subject.keyword Computational models
dc.subject.keyword DNA methylation
dc.subject.keyword Nuclear organization
dc.title Impact of DNA methylation on 3D genome structure
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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