Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2.
- Resource Type
- Academic Journal
- Authors
- Ortega-Alarcon D; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units GBsC-CSIC-BIFI and ICVV-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain.; Claveria-Gimeno R; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units GBsC-CSIC-BIFI and ICVV-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain.; Vega S; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units GBsC-CSIC-BIFI and ICVV-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain.; Jorge-Torres OC; Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain.; Esteller M; Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), l'Hospitalet de Llobregat, 08907 Barcelona, Spain.; Abian O; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units GBsC-CSIC-BIFI and ICVV-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain. Electronic address: oabifra@unizar.es.; Velazquez-Campoy A; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units GBsC-CSIC-BIFI and ICVV-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain; Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain. Electronic address: adrianvc@unizar.es.
- Source
- Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
- Subject
- Language
- English
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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2023. Published by Elsevier B.V.)