Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2

Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark recognized by methyl-CpG binding protein 2 (MeCP2), which acts as a transcriptional regulator and a global chromatin-remodeling element. Because 5hmC triggers a gene regulation response markedly different from that produced by methyla...

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Autores: Ortega Alarcon, David, Claveria Gimeno, Rafael, Vega, Sonia, Jorge Torres, Olga C., Esteller, Manel, Abian, Olga, Velazquez Campoy, Adrian
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:153217
Acceso en línea:http://zaguan.unizar.es/record/153217
Access Level:acceso abierto
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spelling Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2Ortega Alarcon, DavidClaveria Gimeno, RafaelVega, SoniaJorge Torres, Olga C.Esteller, ManelAbian, OlgaVelazquez Campoy, AdrianHydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark recognized by methyl-CpG binding protein 2 (MeCP2), which acts as a transcriptional regulator and a global chromatin-remodeling element. Because 5hmC triggers a gene regulation response markedly different from that produced by methylated cytosine (5mC), both modifications must affect DNA structure and/or DNA interaction with MeCP2 differently. MeCP2 is a six-domain intrinsically disordered protein (IDP) with two domains responsible for dsDNA binding: methyl-CpG binding domain (MBD) and intervening domain (ID). Here we report the detailed thermodynamic characterization of the interaction of hmCpG-DNA with MeCP2. We find that hmCpG-DNA interacts with MeCP2 in a distinctly different mode with a particular thermodynamic signature, compared to methylated or unmethylated DNA. In addition, we find evidence for Rett syndrome-associated mutations altering the interaction of MeCP2 with dsDNA in a cytosine modification-specific manner which may correlate with disease onset time and clinical severity score.2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://zaguan.unizar.es/record/153217reponame:Zaguán. Repositorio Digital de la Universidad de Zaragozainstname:Universidad de ZaragozaInglésinfo:eu-repo/grantAgreement/ES/DGA/B25-20Rinfo:eu-repo/grantAgreement/ES/DGA/E45-20Rinfo:eu-repo/grantAgreement/ES/ISCIII/CIBERehdinfo:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your futureinfo:eu-repo/grantAgreement/ES/MICINN/AEIinfo:eu-repo/grantAgreement/ES/MINECO/FEDERinfo:eu-repo/semantics/openAccessoai:zaguan.unizar.es:1532172026-05-29T13:59:51Z
dc.title.none.fl_str_mv Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
title Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
spellingShingle Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
Ortega Alarcon, David
title_short Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
title_full Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
title_fullStr Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
title_full_unstemmed Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
title_sort Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
dc.creator.none.fl_str_mv Ortega Alarcon, David
Claveria Gimeno, Rafael
Vega, Sonia
Jorge Torres, Olga C.
Esteller, Manel
Abian, Olga
Velazquez Campoy, Adrian
author Ortega Alarcon, David
author_facet Ortega Alarcon, David
Claveria Gimeno, Rafael
Vega, Sonia
Jorge Torres, Olga C.
Esteller, Manel
Abian, Olga
Velazquez Campoy, Adrian
author_role author
author2 Claveria Gimeno, Rafael
Vega, Sonia
Jorge Torres, Olga C.
Esteller, Manel
Abian, Olga
Velazquez Campoy, Adrian
author2_role author
author
author
author
author
author
description Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark recognized by methyl-CpG binding protein 2 (MeCP2), which acts as a transcriptional regulator and a global chromatin-remodeling element. Because 5hmC triggers a gene regulation response markedly different from that produced by methylated cytosine (5mC), both modifications must affect DNA structure and/or DNA interaction with MeCP2 differently. MeCP2 is a six-domain intrinsically disordered protein (IDP) with two domains responsible for dsDNA binding: methyl-CpG binding domain (MBD) and intervening domain (ID). Here we report the detailed thermodynamic characterization of the interaction of hmCpG-DNA with MeCP2. We find that hmCpG-DNA interacts with MeCP2 in a distinctly different mode with a particular thermodynamic signature, compared to methylated or unmethylated DNA. In addition, we find evidence for Rett syndrome-associated mutations altering the interaction of MeCP2 with dsDNA in a cytosine modification-specific manner which may correlate with disease onset time and clinical severity score.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://zaguan.unizar.es/record/153217
url http://zaguan.unizar.es/record/153217
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/ES/DGA/B25-20R
info:eu-repo/grantAgreement/ES/DGA/E45-20R
info:eu-repo/grantAgreement/ES/ISCIII/CIBERehd
info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017
info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
info:eu-repo/grantAgreement/ES/MICINN/AEI
info:eu-repo/grantAgreement/ES/MINECO/FEDER
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv
publisher.none.fl_str_mv
dc.source.none.fl_str_mv reponame:Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname:Universidad de Zaragoza
instname_str Universidad de Zaragoza
reponame_str Zaguán. Repositorio Digital de la Universidad de Zaragoza
collection Zaguán. Repositorio Digital de la Universidad de Zaragoza
repository.name.fl_str_mv
repository.mail.fl_str_mv
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