@article{40646068e98a46a7b5ecff8ffbfb5e73,
title = "Critical Role of Histone Turnover in Neuronal Transcription and Plasticity",
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.",
author = "Ian Maze and Wendy Wenderski and Noh, {Kyung Min} and Bagot, {Rosemary C.} and Nikos Tzavaras and Immanuel Purushothaman and Els{\"a}sser, {Simon J.} and Yin Guo and Carolina Ionete and Hurd, {Yasmin L.} and Tamminga, {Carol A.} and Tobias Halene and Lorna Farrelly and Soshnev, {Alexey A.} and Duancheng Wen and Shahin Rafii and Birtwistle, {Marc R.} and Schahram Akbarian and Buchholz, {Bruce A.} and Blitzer, {Robert D.} and Nestler, {Eric J.} and Yuan, {Zuo Fei} and Garcia, {Benjamin A.} and Li Shen and Henrik Molina and Allis, {C. David}",
note = "Funding Information: We would like to thank members of the C.D.A. laboratory for critical readings of the manuscript and contribution of reagents (particularly Dr. Ronen Sadeh). We would also like to thank Dr. Kunihiro Uryu (The Rockefeller University Electron Microscopy Resource Center) for assistance with TEM experiments, Ms. Kelly Gleason for help with human postmortem brain dissections, and Mr. Charlie Li for assistance with mESC FACS. This work was supported by grants from the National Institute of Mental Health (NIMH) : 5R01 MH094698 and P50 MH096890 . B.A.G. gratefully acknowledges funding from the following NIH grants: R21MH102679 and RO1GM110174 . Support for accelerator mass spectrometry analyses was provided by NIH 8P41GM103483 . This work was performed, in part, under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under contracts DE-AC52-07NA27344 and LLNL-JRNL-653296 . Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jul,
day = "1",
doi = "10.1016/j.neuron.2015.06.014",
language = "English",
volume = "87",
pages = "77--94",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",
}