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dc.contributor.authorBattistini, Federica
dc.contributor.authorDans, Pablo D
dc.contributor.authorTerrazas, Montserrat
dc.contributor.authorCastellazzi, Chiara L
dc.contributor.authorPortella, Guillem
dc.contributor.authorLabrador, Mireia
dc.contributor.authorVillegas, Núria
dc.contributor.authorBrun-Heath, Isabelle
dc.contributor.authorGonzález, Carlos
dc.contributor.authorOrozco, Modesto
dc.date.accessioned2022-01-07T13:12:26Z
dc.date.available2022-01-07T13:12:26Z
dc.date.issued2021-11
dc.identifier.issn1553-734X
dc.identifier.otherPMC8601608
dc.identifier.other34748533
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332300
dc.descriptionFunder: Programa de Desarrollo de las Ciencias Basicas
dc.descriptionFunder: Institució Catalana de Recerca i Estudis Avancats
dc.descriptionFunder: Sistema Nacional de Investigadores, Agencia Nacional de Investigación e Innovación, Uruguay
dc.descriptionFunder: Government of Spain
dc.description.abstractWe present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties similar to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) generally lead to stiffer DNA than normal cytosine, with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). Conversely, our simulations suggest that methylated-DNA binding domains (MBDs), associated with repression activities, are sensitive to the substitution d(mCpG) ➔ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) d(hmCpG) change. Overall, while gene activity changes due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding.
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1553-7358
dc.sourcenlmid: 101238922
dc.titleThe Impact of the HydroxyMethylCytosine epigenetic signature on DNA structure and function.
dc.typeArticle
dc.date.updated2022-01-07T13:12:25Z
prism.issueIdentifier11
prism.publicationNamePLoS Comput Biol
prism.volume17
dc.identifier.doi10.17863/CAM.79747
dcterms.dateAccepted2021-10-10
rioxxterms.versionofrecord10.1371/journal.pcbi.1009547
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBattistini, Federica [0000-0002-7544-0938]
dc.contributor.orcidDans, Pablo D [0000-0002-5927-372X]
dc.contributor.orcidTerrazas, Montserrat [0000-0001-8614-5777]
dc.contributor.orcidLabrador, Mireia [0000-0002-7105-1054]
dc.contributor.orcidVillegas, Núria [0000-0001-9323-0697]
dc.contributor.orcidBrun-Heath, Isabelle [0000-0002-5828-0020]
dc.contributor.orcidGonzález, Carlos [0000-0001-8796-1282]
dc.identifier.eissn1553-7358
pubs.funder-project-idspanish ministry of science (RTI2018-096704-B-100, BFU2017-89707-P)
pubs.funder-project-idCatalan goverment (SGR2017-134)
pubs.funder-project-idInstituto de Salud Carlos III (ISCIII PT 17/0009/0007)
pubs.funder-project-idH2020 European Research Council, BIOEXCEL2 (823830)
pubs.funder-project-idEuropean Research Council (823830)
cam.issuedOnline2021-11-08


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International