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.
Highlights
The cellular composition and connectivity of vertebrate sensory systems are shaped by signals from the external environment
We have shown here that the activity-dependent replacement of canonical H2B with H2BE, an olfactory-specific histone variant, has a direct impact on the gene expression and life span of olfactory sensory neurons
The repertoire of expressed olfactory receptor (OR) in the main olfactory epithelium (MOE) is determined by the combined probabilities associated with the choice of a specific OR by olfactory neuron precursors and the subsequent longevity of those neurons
Summary
The cellular composition and connectivity of vertebrate sensory systems are shaped by signals from the external environment. Experience-dependent plasticity has been shown to participate in the functional matur ation of other sensory systems, including the auditory, somatosensory, and olfactory systems (Hensch, 2004). In addition to their important role in shaping sensory circuits during development, environmental stimuli can significantly affect adult brain structures, leading to adaptive as well as maladaptive changes in sensory responses (Buonomano and Merzenich, 1998; Ramachandran and Hirstein, 1998; Moseley and Flor, 2012). A molecular-level understanding of these changes is far from complete, synaptic refinement and activity-dependent transcriptional changes appear to play prominent roles (Holtmaat and Svoboda, 2009; Dulac, 2010; Riccio, 2010; West and Greenberg, 2011)
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