| First Author | Maze I | Year | 2015 |
| Journal | Neuron | Volume | 87 |
| Issue | 1 | Pages | 77-94 |
| PubMed ID | 26139371 | Mgi Jnum | J:356262 |
| Mgi Id | MGI:7762354 | Doi | 10.1016/j.neuron.2015.06.014 |
| Citation | Maze I, et al. (2015) Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron 87(1):77-94 |
| abstractText | Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation-associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity, and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near-saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3-containing nucleosomes remain highly dynamic-in a modification-independent manner-to control neuronal- and glial-specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical and previously undocumented regulator of cell type-specific transcription and plasticity in mammalian brain. |
