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http://hdl.handle.net/2445/155228
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DC Field | Value | Language |
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dc.contributor.author | Martínez de Paz, Alexia | - |
dc.contributor.author | Khajavi, Leila | - |
dc.contributor.author | Martin, Hélène | - |
dc.contributor.author | Clavería Gimeno, Rafael | - |
dc.contributor.author | Dieck, Susanne Tom | - |
dc.contributor.author | Cheema, Manjinder | - |
dc.contributor.author | Sanchez-Mut, Jose Vicente | - |
dc.contributor.author | Moksa, Malgorzata M. | - |
dc.contributor.author | Carles, Annaick | - |
dc.contributor.author | Brodie, Nick I. | - |
dc.contributor.author | Sheikh, Taimoor I. | - |
dc.contributor.author | Freeman, Melissa E. | - |
dc.contributor.author | Petrotchenko, Evgeniy V. | - |
dc.contributor.author | Borchers, Christoph H. | - |
dc.contributor.author | Schuman, Erin M. | - |
dc.contributor.author | Zytnicki, Matthias | - |
dc.contributor.author | Velazquez-Campoy, Adrian | - |
dc.contributor.author | Abian, Olga | - |
dc.contributor.author | Hirst, Martin | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Vincent, John B. | - |
dc.contributor.author | Malnou, Cécile E. | - |
dc.contributor.author | Ausió, Juan | - |
dc.date.accessioned | 2020-04-14T10:07:48Z | - |
dc.date.available | 2020-04-14T10:07:48Z | - |
dc.date.issued | 2019-10-10 | - |
dc.identifier.issn | 1756-8935 | - |
dc.identifier.uri | http://hdl.handle.net/2445/155228 | - |
dc.description.abstract | 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. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s13072-019-0298-1 | - |
dc.relation.ispartof | Epigenetics & Chromatin, 2019, vol. 12, num. 1, p. 63 | - |
dc.relation.uri | https://doi.org/10.1186/s13072-019-0298-1 | - |
dc.rights | cc-by (c) Martínez de Paz, Alexia et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Cromatina | - |
dc.subject.classification | Síndrome de Rett | - |
dc.subject.classification | ADN | - |
dc.subject.other | Chromatin | - |
dc.subject.other | Rett syndrome | - |
dc.subject.other | DNA | - |
dc.title | MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 695392 | - |
dc.date.updated | 2020-04-14T10:07:49Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/743216/EU//NeuroRibo | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/268626/EU//EPINORC | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/727264/EU//EPIPHARM | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31601272 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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695392.pdf | 6.83 MB | Adobe PDF | View/Open |
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