Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation
Open accessAbstract
Activity-dependent modifications of chromatin are believed to contribute to dramatic changes in neuronal circuitry. The mechanisms underlying these modifications are not fully understood. The histone variant H3.3 is incorporated in a replication-independent manner into different regions of the genome, including gene regulatory elements. It is presently unknown whether H3.3 deposition is involved in neuronal activity-dependent events. Here, we analyze the role of the histone chaperone DAXX in the regulation of H3.3 incorporation at activity-dependent gene loci. DAXX is found to be associated with regulatory regions of selected activity-regulated genes, where it promotes H3.3 loading upon membrane depolarization. DAXX loss not only affects H3.3 deposition but also impairs transcriptional induction of these genes. Calcineurin-mediated dephosphorylation of DAXX is a key molecular switch controlling its function upon neuronal activation. Overall, these findings implicate the H3.3 chaperone DAXX in the regulation of activity-dependent events, thus revealing a new mechanism underlying epigenetic modifications in neurons.
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H3.3 is the predominant H3 variant mutated in pediatric high-grade gliomas.
“H3.3 is the predominant H3 variant mutated in pHGG”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Michod et al., 2012
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References 72 · Cited by 93
- Authors
- Michod, D., Bartesaghi, S., Khelifi, A., Bellodi, C., Berliocchi, L., Nicotera, P., & Salomoni, P.
- Affiliations
- University College London (GB)
- Medical Research Council (GB)
- University of California, San Francisco (US)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Salomoni, Paolo
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 74
- Issue
- 1
- Pages
- 122-135
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3657165
- OpenAlex
- W2044459308
- Cited by
- 93
- References
- 72
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 11 · 2015: 12 · 2014: 6 · 2013: 8 · 2012: 3
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- Harvard University
- Wellcome Trust
- University College London
- Brain Tumour Charity
- Università degli Studi del Piemonte Orientale
- Université de Lausanne
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- DAXX, histone chaperone, histone H3.3, histone variant deposition, calcineurin, dephosphorylation, neuronal activity, activity-dependent gene regulation, transcriptional induction, membrane depolarization, epigenetic regulation, chromatin modification
- MeSH terms
- Animals, Calcium, Carrier Proteins, Cerebral Cortex, Gene Expression Regulation, Histones, Membrane Potentials, Nerve Net, Neural Conduction, Neurons, Nuclear Proteins, Transcription, Genetic, Genes, Immediate-Early, Mice, Knockout, Molecular Chaperones, Calcineurin, Epigenesis, Genetic, Intracellular Signaling Peptides and Proteins, Mice, Histone Chaperones, Co-Repressor Proteins
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