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Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation.

Michod, D; Bartesaghi, S; Khelifi, A; Bellodi, C; Berliocchi, L; Nicotera, P; Salomoni, P; (2012) Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron , 74 (1) 122 - 135. 10.1016/j.neuron.2012.02.021. Green open access

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Abstract

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.

Type: Article
Title: Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation.
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuron.2012.02.021
Publisher version: http://dx.doi.org/10.1016/j.neuron.2012.02.021
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3657165
Keywords: Animals, Calcineurin, Calcium, Carrier Proteins, Cerebral Cortex, Epigenesis, Genetic, Gene Expression Regulation, Genes, Immediate-Early, Histone Chaperones, Histones, Intracellular Signaling Peptides and Proteins, Membrane Potentials, Mice, Mice, Knockout, Nerve Net, Neural Conduction, Neurons, Nuclear Proteins, Transcription, Genetic
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/1344622
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