The activity-dependent histone variant H2BE modulates the life span of olfactory neurons

Elife. 2012 Dec 13;1:e00070. doi: 10.7554/eLife.00070.

Abstract

We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment.DOI:http://dx.doi.org/10.7554/eLife.00070.001.

Keywords: Mouse; epigenetics; histone; olfactory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Death / genetics
  • Gene Expression
  • HEK293 Cells
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Odorants / analysis
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / metabolism*
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / metabolism*
  • Protein Processing, Post-Translational*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Smell / genetics*

Substances

  • Histones
  • Recombinant Fusion Proteins