153217 20251017144635.0 doi 10.1016/j.ijbiomac.2023.123373 sideral 133170 ART-2023-133170 eng Ortega Alarcon, David (orcid)0000-0003-1885-4365 Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2 2023 Access copy available to the general public Unrestricted 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. 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/PID2021-127296OB-I00 info:eu-repo/grantAgreement/ES/MINECO/FEDER/BFU2016-78232-P info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 7.7 2023 BIOCHEMISTRY & MOLECULAR BIOLOGY 34 / 313 = 0.109 2023 Q1 T1 POLYMER SCIENCE 6 / 95 = 0.063 2023 Q1 T1 CHEMISTRY, APPLIED 6 / 74 = 0.081 2023 Q1 T1 1.245 2023 Biochemistry 2023 Q1 Structural Biology 2023 Q2 Molecular Biology 2023 Q2 13.7 2023 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Claveria Gimeno, Rafael Vega, Sonia Jorge Torres, Olga C. Esteller, Manel Abian, Olga Universidad de Zaragoza (orcid)0000-0001-5664-1729 Velazquez Campoy, Adrian Universidad de Zaragoza (orcid)0000-0001-5702-4538 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 232 (2023), 123373 [13 pp] Int. j. biol. macromol. International journal of biological macromolecules 0141-8130 2147726 http://zaguan.unizar.es/record/153217/files/texto_completo.pdf Postprint 1952962 http://zaguan.unizar.es/record/153217/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:153217 articulos driver 2025-10-17-14:28:37 ARTICLE