{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:09:51Z","timestamp":1792145391977,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Science Departments of the Catalan Government"},{"name":"Catalan and the Spanish Associations for Rett Syndrome"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) is a severe neurodevelopmental disease caused almost exclusively by mutations to the MeCP2 gene. This disease may be regarded as a synaptopathy, with impairments affecting synaptic plasticity, inhibitory and excitatory transmission and network excitability. The complete understanding of the mechanisms behind how the transcription factor MeCP2 so profoundly affects the mammalian brain are yet to be determined. What is known, is that MeCP2 involvement in activity-dependent expression programs is a critical link between this protein and proper neuronal activity, which allows the correct maturation of connections in the brain. By using RNA-sequencing analysis, we found several immediate-early genes (IEGs, key mediators of activity-dependent responses) directly bound by MeCP2 at the chromatin level and upregulated in the hippocampus and prefrontal cortex of the Mecp2-KO mouse. Quantification of the IEGs response to stimulus both in vivo and in vitro detected an aberrant expression pattern in MeCP2-deficient neurons. Furthermore, altered IEGs levels were found in RTT patient\u2019s peripheral blood and brain regions of post-mortem samples, correlating with impaired expression of downstream myelination-related genes. Altogether, these data indicate that proper IEGs expression is crucial for correct synaptic development and that MeCP2 has a key role in the regulation of IEGs.<\/jats:p>","DOI":"10.3390\/ijms24021453","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T01:32:26Z","timestamp":1673487146000},"page":"1453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Global Impairment of Immediate-Early Genes Expression in Rett Syndrome Models and Patients Linked to Myelination Defects"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-2895","authenticated-orcid":false,"given":"Paolo","family":"Petazzi","sequence":"first","affiliation":[{"name":"Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Carrer Casanova 143, 400\u00b0 floor, 08036 Barcelona, Spain"},{"name":"RICORS-TERAV, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-8865","authenticated-orcid":false,"given":"Olga Caridad","family":"Jorge-Torres","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gomez","sequence":"additional","affiliation":[{"name":"Biosciences Department, Faculty of Sciences and Technology (FCT), University of Vic-Central University of Catalonia (UVic-UCC), C. de la Laura, 13, 08500 Vic, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Scognamiglio","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Serra-Musach","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5164-6803","authenticated-orcid":false,"given":"Angelika","family":"Merkel","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grases","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-554X","authenticated-orcid":false,"given":"Clara","family":"Xiol","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n San Juan de Dios, 08950 Barcelona, Spain"},{"name":"Servei de Medicina Gen\u00e8tica i Molecular, Institut de Recerca Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1896-1622","authenticated-orcid":false,"given":"Mar","family":"O\u2019Callaghan","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Rett, Neurology Department, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"CIBER-ER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-9307","authenticated-orcid":false,"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Servei de Medicina Gen\u00e8tica i Molecular, Institut de Recerca Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"CIBER-ER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-6093","authenticated-orcid":false,"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain"},{"name":"Centro de Investigacion Biomedica en Red Cancer (CIBERONC), 28029 Madrid, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), 08010 Barcelona, Spain"},{"name":"Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2257-3331","authenticated-orcid":false,"given":"Sonia","family":"Guil","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916 Barcelona, Spain"},{"name":"Germans Trias i Pujol Health Science Research Institute, Badalona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrg3897","article-title":"Rett syndrome: A complex disorder with simple roots","volume":"16","author":"Lyst","year":"2015","journal-title":"Nat. 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