Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/155228
Title: | MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2 |
Author: | Martínez de Paz, Alexia Khajavi, Leila Martin, Hélène Clavería Gimeno, Rafael Dieck, Susanne Tom Cheema, Manjinder Sanchez-Mut, Jose Vicente Moksa, Malgorzata M. Carles, Annaick Brodie, Nick I. Sheikh, Taimoor I. Freeman, Melissa E. Petrotchenko, Evgeniy V. Borchers, Christoph H. Schuman, Erin M. Zytnicki, Matthias Velazquez-Campoy, Adrian Abian, Olga Hirst, Martin Esteller, Manel Vincent, John B. Malnou, Cécile E. Ausió, Juan |
Keywords: | Cromatina Síndrome de Rett ADN Chromatin Rett syndrome DNA |
Issue Date: | 10-Oct-2019 |
Publisher: | BioMed Central |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1186/s13072-019-0298-1 |
It is part of: | Epigenetics & Chromatin, 2019, vol. 12, num. 1, p. 63 |
URI: | http://hdl.handle.net/2445/155228 |
Related resource: | https://doi.org/10.1186/s13072-019-0298-1 |
ISSN: | 1756-8935 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
695392.pdf | 6.83 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License