Function of an Olfactory-specific Histone Variant: We Are What We Smell?

We identified a replication-independent histone variant, Hist2h2be (referred to as H2be), that in mice is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE protein were found to be heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain-
and loss-of-function experiments demonstrated that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. Sensory deprivation and stimulation experiments showed 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. We found that post-translational modifications 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.