The histone demethylase PHF8 regulates astrocyte differentiation and function.
Animals
Astrocytes
/ cytology
Binding Sites
Biomarkers
Cell Differentiation
/ genetics
Cell Proliferation
Gene Expression Profiling
Gene Expression Regulation
Histone Demethylases
/ genetics
Histones
/ metabolism
Mice
Models, Biological
Neurogenesis
Neurons
/ metabolism
Protein Binding
Synapses
/ metabolism
Transcription Factors
/ genetics
Transcription, Genetic
Astrocyte differentiation
Chromatin transcription
Histone demethylation
PHF8
Synapse
XLID
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 06 2021
15 06 2021
Historique:
received:
17
07
2020
accepted:
15
04
2021
pubmed:
4
6
2021
medline:
3
8
2021
entrez:
3
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34081130
pii: 268981
doi: 10.1242/dev.194951
pii:
doi:
Substances chimiques
Biomarkers
0
Histones
0
Transcription Factors
0
Histone Demethylases
EC 1.14.11.-
PHF8 protein, mouse
EC 1.14.11.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministry of Economy
ID : PGC2018-096082-B-I00
Organisme : Ministerio de Economía, Industria y Competitividad, Gobierno de España
ID : BFU2015-69248-P
Organisme : Boehringer Ingelheim
Organisme : Ministerio de Ciencia e Innovación de España
ID : PID2019-111217RB-I00
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.