The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function

We 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 p...

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Detalles Bibliográficos
Autores: Battistini, Federica, Dans, Pablo D., Terrazas Martínez, Montserrat, Castellazzi, Chiara L., Portella, Guillem, Labrador, Mireia, Villegas, Núria, Brun Heath, Isabelle, González, Carlos, Orozco López, Modesto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/187248
Acceso en línea:https://hdl.handle.net/2445/187248
Access Level:acceso abierto
Palabra clave:Epigenètica
ADN
Translocació (Genètica)
Epigenetics
DNA
Translocation (Genetics)
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spelling The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and functionBattistini, FedericaDans, Pablo D.Terrazas Martínez, MontserratCastellazzi, Chiara L.Portella, GuillemLabrador, MireiaVillegas, NúriaBrun Heath, IsabelleGonzález, CarlosOrozco López, ModestoEpigenèticaADNTranslocació (Genètica)EpigeneticsDNATranslocation (Genetics)We 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.Public Library of Science (PLoS)2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/187248Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1009547PLoS Computational Biology, 2021, vol. 17, num. 11, p. e1009547https://doi.org/10.1371/journal.pcbi.1009547info:eu-repo/grantAgreement/EC/H2020/823830cc-by (c) Battistini, Federica et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1872482026-05-27T06:46:51Z
dc.title.none.fl_str_mv The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
title The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
spellingShingle The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
Battistini, Federica
Epigenètica
ADN
Translocació (Genètica)
Epigenetics
DNA
Translocation (Genetics)
title_short The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
title_full The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
title_fullStr The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
title_full_unstemmed The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
title_sort The impact of the hydroxymethylcytosine epigenetic signature on DNA structure and function
dc.creator.none.fl_str_mv Battistini, Federica
Dans, Pablo D.
Terrazas Martínez, Montserrat
Castellazzi, Chiara L.
Portella, Guillem
Labrador, Mireia
Villegas, Núria
Brun Heath, Isabelle
González, Carlos
Orozco López, Modesto
author Battistini, Federica
author_facet Battistini, Federica
Dans, Pablo D.
Terrazas Martínez, Montserrat
Castellazzi, Chiara L.
Portella, Guillem
Labrador, Mireia
Villegas, Núria
Brun Heath, Isabelle
González, Carlos
Orozco López, Modesto
author_role author
author2 Dans, Pablo D.
Terrazas Martínez, Montserrat
Castellazzi, Chiara L.
Portella, Guillem
Labrador, Mireia
Villegas, Núria
Brun Heath, Isabelle
González, Carlos
Orozco López, Modesto
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenètica
ADN
Translocació (Genètica)
Epigenetics
DNA
Translocation (Genetics)
topic Epigenètica
ADN
Translocació (Genètica)
Epigenetics
DNA
Translocation (Genetics)
description We 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/187248
url https://hdl.handle.net/2445/187248
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1009547
PLoS Computational Biology, 2021, vol. 17, num. 11, p. e1009547
https://doi.org/10.1371/journal.pcbi.1009547
info:eu-repo/grantAgreement/EC/H2020/823830
dc.rights.none.fl_str_mv cc-by (c) Battistini, Federica et al., 2021
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Battistini, Federica et al., 2021
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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