86342 20210507081950.0 doi 10.1186/s13072-019-0298-1 sideral 114916 ART-2019-114916 eng Martínez De Paz, A. MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2 2019 Access copy available to the general public Unrestricted Background: MeCP2- A chromatin-binding protein associated with Rett syndrome-has two main isoforms, MeCP2-E1 and MeCP2-E2, differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, in addition to their different cellular localization and differential expression during brain development, suggest that they may also have non-overlapping molecular mechanisms. However, differential functions of MeCP2-E1 and E2 remain largely unexplored. Results: Here, we show that the N-terminal domains (NTD) of MeCP2-E1 and E2 modulate the ability of the methyl-binding domain (MBD) to interact with DNA as well as influencing the turn-over rates, binding dynamics, response to neuronal depolarization, and circadian oscillations of the two isoforms. Our proteomics data indicate that both isoforms exhibit unique interacting protein partners. Moreover, genome-wide analysis using ChIP-seq provide evidence for a shared as well as a specific regulation of different sets of genes. Conclusions: Our study supports the idea that Rett syndrome might arise from simultaneous impairment of cellular processes involving non-overlapping functions of MECP2 isoforms. For instance, MeCP2-E1 mutations might impact stimuli-dependent chromatin regulation, while MeCP2-E2 mutations could result in aberrant ribosomal expression. Overall, our findings provide insight into the functional complexity of MeCP2 by dissecting differential aspects of its two isoforms. info:eu-repo/grantAgreement/EUR/ERC/NeuroRibo-743216 info:eu-repo/grantAgreement/EUR/ERC-EPINORC-268626 info:eu-repo/grantAgreement/ES/FIS/PI15-00663 info:eu-repo/grantAgreement/EC/H2020/727264/EU/Development of a ncRNA DNA Methylation Kit for Treatment Guidance in Cancer of Unknown Primary/EPIPHARM This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 727264-EPIPHARM info:eu-repo/grantAgreement/ES/ISCIII/CB16-12-00312 info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017 info:eu-repo/grantAgreement/ES/ISCIII/RD12-0036-0039 info:eu-repo/grantAgreement/ES/MEC/FPU13-3870 info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/grantAgreement/ES/MINECO/SAF2014-55000-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.237 2019 GENETICS & HEREDITY 41 / 177 = 0.232 2019 Q1 T1 2.449 2019 Molecular Biology 2019 Q1 Genetics 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Khajavi, L. Martin, H. Claveria-Gimeno, R. Tom Dieck, S. Cheema, M.S. Sanchez-Mut, J.V. Moksa, M.M. Carles, A. Brodie, N.I. Sheikh, T.I. Freeman, M.E. Petrotchenko, E.V. Borchers, C.H. Schuman, E.M. Zytnicki, M. Velazquez-Campoy, A. Universidad de Zaragoza (orcid)0000-0001-5702-4538 Abian, O. Universidad de Zaragoza (orcid)0000-0001-5664-1729 Hirst, M. Esteller, M. Vincent, J.B. Malnou, C.E. Ausió, J. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12, 63 (2019), s13072-019-0298-1 [16 pp.] EPIGENETICS & CHROMATIN EPIGENETICS & CHROMATIN 1756-8935 6931228 http://zaguan.unizar.es/record/86342/files/texto_completo.pdf Versión publicada 84561 http://zaguan.unizar.es/record/86342/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:86342 articulos driver 2021-05-07-08:11:34 ARTICLE