Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2

Ortega Alarcon, David ; Claveria Gimeno, Rafael ; Vega, Sonia ; Jorge Torres, Olga C. ; Esteller, Manel ; Abian, Olga (Universidad de Zaragoza) ; Velazquez Campoy, Adrian (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.ijbiomac.2023.123373

Año: 2023

Publicado en: International journal of biological macromolecules 232 (2023), 123373 [13 pp]
ISSN: 0141-8130

Factor impacto JCR: 7.7 (2023)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 34 / 313 = 0.109 (2023) - Q1 - T1
Categ. JCR: POLYMER SCIENCE rank: 6 / 95 = 0.063 (2023) - Q1 - T1
Categ. JCR: CHEMISTRY, APPLIED rank: 6 / 74 = 0.081 (2023) - Q1 - T1

Factor impacto CITESCORE: 13.7 - Molecular Biology (Q1) - Food Science (Q1) - Structural Biology (Q1) - Biomaterials (Q1) - Biochemistry (Q1)

Factor impacto SCIMAGO: 1.245 - Biochemistry (Q1) - Structural Biology (Q2) - Molecular Biology (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CIBERehd
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/FEDER/BFU2016-78232-P

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)