Details

Autor(en) / Beteiligte

• Maze, Ian
• Wenderski, Wendy
• Noh, Kyung-Min
• Bagot, Rosemary C.
• Tzavaras, Nikos
• Purushothaman, Immanuel
• Elsässer, Simon J.
• Guo, Yin
• Ionete, Carolina
• Hurd, Yasmin L.
• Tamminga, Carol A.
• Halene, Tobias
• Farrelly, Lorna
• Soshnev, Alexey A.
• Wen, Duancheng
• Rafii, Shahin
• Birtwistle, Marc R.
• Akbarian, Schahram
• Buchholz, Bruce A.
• Blitzer, Robert D.
• Nestler, Eric J.
• Yuan, Zuo-Fei
• Garcia, Benjamin A.
• Shen, Li
• Molina, Henrik
• Allis, C. David

Titel

Critical Role of Histone Turnover in Neuronal Transcription and Plasticity

Ist Teil von

• Neuron (Cambridge, Mass.), 2015-07, Vol.87 (1), p.77-94

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. •H3.3 displays a unique saturating profile of nucleosome occupancy in postnatal brain•Histones turn over rapidly to promote activity-dependent neuronal transcription•Nucleosomal dynamics are required for synaptic development and behavioral plasticity•Histone turnover is critical for cell type-specific gene expression Maze et al. demonstrate a critical role for histone turnover in the regulation of neuronal transcription and synaptic development. Histone dynamics are essential for cognitive plasticity and represent a novel epigenetic mechanism with far-reaching implications for human neurobiology and disease.