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Título: | MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with diferent protein and DNA interactions compared to MeCP2-E2 |
Autor: | Martínez de Paz, Alexia; Khajavi, Leila; Martin, Hélène; Claveria-Gimeno, Rafael; Dieck, S. T.; Cheema, Manjinder S.; Sánchez-Mut, José V.; Moksa, Malgorzata M.; Carles, Annaick; Brodie, Nick I.; Sheikh, Taimoor I.; Freenan, Melissa E.; Petrotchenko, Evgeniy V.; Borchers, Christoph H.; Schuman, Erin M.; Zytnicki, Matthias; Velázquez-Campoy, Adrián; Abian, Olga CSIC ORCID; Hirst, Martin; Estelller, Manel; Vincent, John B.; Malnou, Cécile E.; Ausió, Juan | Palabras clave: | Chromatin Isoforms mecp2 Rett syndrome |
Fecha de publicación: | 10-oct-2019 | Editor: | Springer Nature | Citación: | Epigenetics & Chromatin 12: 63 (2019) | Resumen: | 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. | Descripción: | 16 pags., 5 figs.-- Open Access funded by Creative Commons Atribution Licence 4.0 | Versión del editor: | https://doi.org/10.1186/s13072-019-0298-1 | URI: | http://hdl.handle.net/10261/204600 | DOI: | 10.1186/s13072-019-0298-1 | ISSN: | 1756-8935 |
Aparece en las colecciones: | (IQF) Artículos |
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Fichero | Descripción | Tamaño | Formato | |
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MeCP2-E1 isoform.pdf | Artículo principal | 6,83 MB | Adobe PDF | Visualizar/Abrir |
13072_2019_298_MOESM1_ESM.tif | Supplementary information | 3,5 MB | TIFF | Visualizar/Abrir |
13072_2019_298_MOESM2_ESM.tif | Supplementary information | 38,85 MB | TIFF | Visualizar/Abrir |
13072_2019_298_MOESM3_ESM.tif | Supplementary information | 2,72 MB | TIFF | Visualizar/Abrir |
13072_2019_298_MOESM4_ESM.tif | Supplementary information | 5,06 MB | TIFF | Visualizar/Abrir |
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