MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2

Simple item page
dc.contributor.authorMartínez de Paz, Alexia
dc.contributor.authorKhajavi, Leila
dc.contributor.authorMartin, Hélène
dc.contributor.authorClaveria‑Gimeno, Rafael
dc.contributor.authorDieck, Susanne Tom
dc.contributor.authorCheema, Manjinder S.
dc.contributor.authorSanchez‑Mut, Jose V.
dc.contributor.authorMoksa, Malgorzata M.
dc.contributor.authorCarles, Annaick
dc.contributor.authorBrodie, Nick I.
dc.contributor.authorSheikh, Taimoor I.
dc.contributor.authorFreeman, Melissa E.
dc.contributor.authorPetrotchenko, Evgeniy V.
dc.contributor.authorBorchers, Christoph H.
dc.contributor.authorSchuman, Erin M.
dc.contributor.authorZytnicki, Matthias
dc.contributor.authorVelazquez‑Campoy, Adrian
dc.contributor.authorAbian, Olga
dc.contributor.authorHirst, Martin
dc.contributor.authoret al.
dc.date.accessioned2020-11-02T23:49:28Z
dc.date.available2020-11-02T23:49:28Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractBackground 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by the Canadian Institutes of Health Research [MOP-130417 to JA and MOP-102758 to JBV]. Genome Canada and Genome British Columbia for financial support for the University of Victoria-Genome BC Proteomics Centre [204PRO and 214PRO], Leading Edge Endowment Fund (University of Victoria), the Segal McGill Chair in Molecular Oncology at McGill University, the Warren Y. Soper Charitable Trust and the Alvin Segal Family Foundation to the Jewish General Hospital to CHB. Max Planck Society and DFG CRC 1080; DFG CRC 902 to EMS. European Research Council under the European Union’s Horizon 2020 research and innovation program [743216 to EMS and 727264 (EPIPHARM) to ME]. Spanish Ministerio de Economia y Competitividad [BFU2013-47064-P and BFU2016-78232-P to AVC and SAF2014- 55000-R to ME]. Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “Investing in your future”) [PI15/00663, and Miguel Servet contract CPII13/0017] to OA. Spanish Ministerio de Educacion Cultura y Deporte [FPU 13/3870] to RCG. Terry Fox Research Institute Program Project [TFRI #1039] and Canadian Cancer Society Research Institute [CCSRI #703489] to MH. European Community’s Seventh Framework Programme (FP7/2007–2013)/ERC [268626/ EPINORC project]; Integrated Project of Excellence [PIE13/00022] (ONCOPROFILE); CIBER 2016 CB16/12/00312 (CIBERONC); the Spanish Cancer Research Network [RD12/0036/0039]; the Cellex Foundation; Obra Social “La Caixa”; and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) AGAUR [2014SGR633] to ME. ME is an ICREA Research Professor. French Association of Rett Syndrome funded research conducted by CEM, HM and LK, genotoul bioinformatics platform Toulouse Midi-Pyrenees (Bioinfo Genotoul) provided computing and storage resources.en_US
dc.identifier.citationMartínez de Paz, A., Khajavi, L., Martin, H., Claveria‑Gimeno, R., Dieck, S. T., Cheema, M. S., … Ausió, J. (2019) MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2. Epigenetics & Chromatin, 12. https://doi.org/10.1186/s13072-019-0298-1en_US
dc.identifier.urihttps://doi.org/10.1186/s13072-019-0298-1
dc.identifier.urihttp://hdl.handle.net/1828/12300
dc.language.isoenen_US
dc.publisherEpigenetics & Chromatinen_US
dc.subjectMeCP2en_US
dc.subjectIsoformsen_US
dc.subjectChromatinen_US
dc.subjectRett syndromeen_US
dc.titleMeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2en_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Martínez_De_Paz_Alexia_EpigenetChromatin_2019.pdf
Size:
6.72 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Faculty Publications (BioMed Central & Faculty of Science)
 
University of Victoria Libraries

We acknowledge and respect the Lək̓ʷəŋən (Songhees and Esquimalt) Peoples on whose territory the university stands, and the Lək̓ʷəŋən and W̱SÁNEĆ Peoples whose historical relationships with the land continue to this day.