Critical Role of Histone Turnover in Neuronal Transcription and Plasticity Academic Article uri icon

Overview

MeSH Major

  • Brain
  • Chromatin
  • Gene Expression Regulation, Developmental
  • Histones
  • Neuronal Plasticity
  • Neurons
  • Nucleosomes

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.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4491146

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2015.06.014

PubMed ID

  • 26139371

Additional Document Info

start page

  • 77

end page

  • 94

volume

  • 87

number

  • 1