000153217 001__ 153217
000153217 005__ 20251017144635.0
000153217 0247_ $$2doi$$a10.1016/j.ijbiomac.2023.123373
000153217 0248_ $$2sideral$$a133170
000153217 037__ $$aART-2023-133170
000153217 041__ $$aeng
000153217 100__ $$0(orcid)0000-0003-1885-4365$$aOrtega Alarcon, David
000153217 245__ $$aUnexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2
000153217 260__ $$c2023
000153217 5060_ $$aAccess copy available to the general public$$fUnrestricted
000153217 5203_ $$aHydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark recognized by methyl-CpG binding protein 2 (MeCP2), which acts as a transcriptional regulator and a global chromatin-remodeling element. Because 5hmC triggers a gene regulation response markedly different from that produced by methylated cytosine (5mC), both modifications must affect DNA structure and/or DNA interaction with MeCP2 differently. MeCP2 is a six-domain intrinsically disordered protein (IDP) with two domains responsible for dsDNA binding: methyl-CpG binding domain (MBD) and intervening domain (ID). Here we report the detailed thermodynamic characterization of the interaction of hmCpG-DNA with MeCP2. We find that hmCpG-DNA interacts with MeCP2 in a distinctly different mode with a particular thermodynamic signature, compared to methylated or unmethylated DNA. In addition, we find evidence for Rett syndrome-associated mutations altering the interaction of MeCP2 with dsDNA in a cytosine modification-specific manner which may correlate with disease onset time and clinical severity score.
000153217 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/CIBERehd$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future$$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00$$9info:eu-repo/grantAgreement/ES/MINECO/FEDER/BFU2016-78232-P
000153217 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000153217 590__ $$a7.7$$b2023
000153217 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b34 / 313 = 0.109$$c2023$$dQ1$$eT1
000153217 591__ $$aPOLYMER SCIENCE$$b6 / 95 = 0.063$$c2023$$dQ1$$eT1
000153217 591__ $$aCHEMISTRY, APPLIED$$b6 / 74 = 0.081$$c2023$$dQ1$$eT1
000153217 592__ $$a1.245$$b2023
000153217 593__ $$aBiochemistry$$c2023$$dQ1
000153217 593__ $$aStructural Biology$$c2023$$dQ2
000153217 593__ $$aMolecular Biology$$c2023$$dQ2
000153217 594__ $$a13.7$$b2023
000153217 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000153217 700__ $$aClaveria Gimeno, Rafael
000153217 700__ $$aVega, Sonia
000153217 700__ $$aJorge Torres, Olga C.
000153217 700__ $$aEsteller, Manel
000153217 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000153217 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez Campoy, Adrian$$uUniversidad de Zaragoza
000153217 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000153217 773__ $$g232 (2023), 123373 [13 pp]$$pInt. j. biol. macromol.$$tInternational journal of biological macromolecules$$x0141-8130
000153217 8564_ $$s2147726$$uhttps://zaguan.unizar.es/record/153217/files/texto_completo.pdf$$yPostprint
000153217 8564_ $$s1952962$$uhttps://zaguan.unizar.es/record/153217/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000153217 909CO $$ooai:zaguan.unizar.es:153217$$particulos$$pdriver
000153217 951__ $$a2025-10-17-14:28:37
000153217 980__ $$aARTICLE