Critical Role of Histone Turnover in Neuronal Transcription and Plasticity

Ian Maze, Wendy Wenderski, Kyung Min Noh, Rosemary C. Bagot, Nikos Tzavaras, Immanuel Purushothaman, Simon J. Elsässer, Yin Guo, Carolina Ionete, Yasmin L. Hurd, Carol A. Tamminga, Tobias Halene, Lorna Farrelly, Alexey A. Soshnev, Duancheng Wen, Shahin Rafii, Marc R. Birtwistle, Schahram Akbarian, Bruce A. Buchholz, Robert D. Blitzer & 6 others Eric J. Nestler, Zuo Fei Yuan, Benjamin A. Garcia, Li Shen, Henrik Molina, C. David Allis

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)77-94
Number of pages18
JournalNeuron
Volume87
Issue number1
DOIs
StatePublished - Jul 1 2015

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Neuronal Plasticity
Histones
Nucleosomes
Brain
Neuroglia
Cognition
Rodentia
Cell Cycle
Genome
Gene Expression
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Maze, I., Wenderski, W., Noh, K. M., Bagot, R. C., Tzavaras, N., Purushothaman, I., ... Allis, C. D. (2015). Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron, 87(1), 77-94. https://doi.org/10.1016/j.neuron.2015.06.014

Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. / 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.

In: Neuron, Vol. 87, No. 1, 01.07.2015, p. 77-94.

Research output: Contribution to journalArticle

Maze, I, Wenderski, W, Noh, KM, Bagot, RC, Tzavaras, N, Purushothaman, I, Elsässer, SJ, Guo, Y, Ionete, C, Hurd, YL, Tamminga, CA, Halene, T, Farrelly, L, Soshnev, AA, Wen, D, Rafii, S, Birtwistle, MR, Akbarian, S, Buchholz, BA, Blitzer, RD, Nestler, EJ, Yuan, ZF, Garcia, BA, Shen, L, Molina, H & Allis, CD 2015, 'Critical Role of Histone Turnover in Neuronal Transcription and Plasticity', Neuron, vol. 87, no. 1, pp. 77-94. https://doi.org/10.1016/j.neuron.2015.06.014
Maze I, Wenderski W, Noh KM, Bagot RC, Tzavaras N, Purushothaman I et al. Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron. 2015 Jul 1;87(1):77-94. https://doi.org/10.1016/j.neuron.2015.06.014
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. / Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. In: Neuron. 2015 ; Vol. 87, No. 1. pp. 77-94.
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