000086342 001__ 86342
000086342 005__ 20210507081950.0
000086342 0247_ $$2doi$$a10.1186/s13072-019-0298-1
000086342 0248_ $$2sideral$$a114916
000086342 037__ $$aART-2019-114916
000086342 041__ $$aeng
000086342 100__ $$aMartínez De Paz, A.
000086342 245__ $$aMeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2
000086342 260__ $$c2019
000086342 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086342 5203_ $$aBackground: 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.
000086342 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-55000-R$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/MEC/FPU13-3870$$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0036-0039$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-0017$$9info:eu-repo/grantAgreement/ES/ISCIII/CB16-12-00312$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 727264-EPIPHARM$$9info:eu-repo/grantAgreement/EC/H2020/727264/EU/Development of a ncRNA DNA Methylation Kit for Treatment Guidance in Cancer of Unknown Primary/EPIPHARM$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/EUR/ERC-EPINORC-268626$$9info:eu-repo/grantAgreement/EUR/ERC/NeuroRibo-743216
000086342 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000086342 590__ $$a4.237$$b2019
000086342 591__ $$aGENETICS & HEREDITY$$b41 / 177 = 0.232$$c2019$$dQ1$$eT1
000086342 592__ $$a2.449$$b2019
000086342 593__ $$aMolecular Biology$$c2019$$dQ1
000086342 593__ $$aGenetics$$c2019$$dQ1
000086342 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000086342 700__ $$aKhajavi, L.
000086342 700__ $$aMartin, H.
000086342 700__ $$aClaveria-Gimeno, R.
000086342 700__ $$aTom Dieck, S.
000086342 700__ $$aCheema, M.S.
000086342 700__ $$aSanchez-Mut, J.V.
000086342 700__ $$aMoksa, M.M.
000086342 700__ $$aCarles, A.
000086342 700__ $$aBrodie, N.I.
000086342 700__ $$aSheikh, T.I.
000086342 700__ $$aFreeman, M.E.
000086342 700__ $$aPetrotchenko, E.V.
000086342 700__ $$aBorchers, C.H.
000086342 700__ $$aSchuman, E.M.
000086342 700__ $$aZytnicki, M.
000086342 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000086342 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, O.$$uUniversidad de Zaragoza
000086342 700__ $$aHirst, M.
000086342 700__ $$aEsteller, M.
000086342 700__ $$aVincent, J.B.
000086342 700__ $$aMalnou, C.E.
000086342 700__ $$aAusió, J.
000086342 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000086342 773__ $$g12, 63 (2019), s13072-019-0298-1 [16 pp.]$$pEPIGENETICS & CHROMATIN$$tEPIGENETICS & CHROMATIN$$x1756-8935
000086342 8564_ $$s6931228$$uhttps://zaguan.unizar.es/record/86342/files/texto_completo.pdf$$yVersión publicada
000086342 8564_ $$s84561$$uhttps://zaguan.unizar.es/record/86342/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000086342 909CO $$ooai:zaguan.unizar.es:86342$$particulos$$pdriver
000086342 951__ $$a2021-05-07-08:11:34
000086342 980__ $$aARTICLE