title: Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation.
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.
authors.affiliation: Samantha Dickson Brain Cancer Unit, University College London Cancer Institute, London WC1E 6DD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Michod
authors.forename: Stefano
authors.initials: S
authors.lastname: Bartesaghi
authors.forename: Amel
authors.initials: A
authors.lastname: Khelifi
authors.forename: Cristian
authors.initials: C
authors.lastname: Bellodi
authors.forename: Laura
authors.initials: L
authors.lastname: Berliocchi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Nicotera
authors.forename: Paolo
authors.initials: P
authors.lastname: Salomoni
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D056970:Co-Repressor Proteins; D044127:Epigenesis, Genetic / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D017781:Genes, Immediate-Early; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism / Q000382:microbiology; D009431:Neural Conduction / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D056488:Histone Chaperones; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019703:Calcineurin; D002118:Calcium