| First Author | Michod D | Year | 2012 |
| Journal | Neuron | Volume | 74 |
| Issue | 1 | Pages | 122-35 |
| PubMed ID | 22500635 | Mgi Jnum | J:188393 |
| Mgi Id | MGI:5440404 | Doi | 10.1016/j.neuron.2012.02.021 |
| Citation | Michod D, et al. (2012) Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron 74(1):122-35 |
| abstractText | 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. |
