dc.contributor
Institut Català de la Salut
dc.contributor
[Iacobucci S, Navarro C, Vicioso-Mantis M] Department of Molecular Genomics, Instituto de Biologıa Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain. [Padilla N, de la Cruz X] Grup de Recerca en Bioinformàtica Clínica i Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institut Català per la Recerca i Estudis Avançats (ICREA), Barcelona 08018, Spain. [Gabrielli M, Lombardi M] CNR Institute of Neuroscience, 20129 Milan, Italy
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Padilla Sirera, Natalia
dc.contributor.author
Gabrielli, Martina
dc.contributor.author
Navarro, Claudia
dc.contributor.author
Lombardi, Marta
dc.contributor.author
Vicioso Mantis, Marta
dc.contributor.author
De la Cruz Montserrat, Fco. Xavier
dc.contributor.author
Iacobucci, Simona
dc.date.accessioned
2025-10-24T08:49:41Z
dc.date.available
2025-10-24T08:49:41Z
dc.date.issued
2022-07-18T14:25:36Z
dc.date.issued
2022-07-18T14:25:36Z
dc.identifier
Iacobucci S, Padilla N, Gabrielli M, Navarro C, Lombardi M, Vicioso-Mantis M, et al. The histone demethylase PHF8 regulates astrocyte differentiation and function. Development. 2021 Jun;148(12):dev194951.
dc.identifier
https://hdl.handle.net/11351/7798
dc.identifier
10.1242/dev.194951
dc.identifier
000681366400005
dc.identifier.uri
http://hdl.handle.net/11351/7798
dc.description.abstract
Astrocyte differentiation; Chromatin transcription; Synapse
dc.description.abstract
Diferenciación de astrocitos; Transcripción de la cromatina; Sinapsis
dc.description.abstract
Diferenciació d'astròcits; Transcripció de la cromatina; Sinapsi
dc.description.abstract
Epigenetic factors have been shown to play a crucial role in X-linked intellectual disability (XLID). Here, we investigate the contribution of the XLID-associated histone demethylase PHF8 to astrocyte differentiation and function. Using genome-wide analyses and biochemical assays in mouse astrocytic cultures, we reveal a regulatory crosstalk between PHF8 and the Notch signaling pathway that balances the expression of the master astrocytic gene Nfia. Moreover, PHF8 regulates key synaptic genes in astrocytes by maintaining low levels of H4K20me3. Accordingly, astrocytic-PHF8 depletion has a striking effect on neuronal synapse formation and maturation in vitro. These data reveal that PHF8 is crucial in astrocyte development to maintain chromatin homeostasis and limit heterochromatin formation at synaptogenic genes. Our studies provide insights into the involvement of epigenetics in intellectual disability.
dc.description.abstract
This study was supported by grants from the Spanish Ministry of Economy (Ministerio de Economía, Industria y Competitividad, Gobierno de España; BFU2015-69248-P and PGC2018-096082-B-I00 to M.A.M.-B.) and Ministerio de Ciencia e Innovación (PID2019-111217RB-I00 to X.C) and a Travelling Fellowship from Boehringer Ingelheim to S.I. Open access funding provided by Consejo Superior de Investigaciones Científicas. Deposited in PMC for immediate release.
dc.format
application/pdf
dc.publisher
Company of Biologists
dc.relation
Development;148(12)
dc.relation
https://doi.org/10.1242/dev.194951
dc.relation
info:eu-repo/grantAgreement/ES/PE2017-2020/PID2019-111217RB-I00
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH Group Donors::Oxidoreductases, N-Demethylating::Histone Demethylases
dc.subject
Other subheadings::Other subheadings::Other subheadings::/genetics
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::oxidorreductasas::oxidorreductasas que actúan sobre donantes de grupos CH-NH::oxidorreductasas N-desmetilantes::histona desmetilasas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/genética
dc.title
The histone demethylase PHF8 regulates astrocyte differentiation and function
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
