Abstract

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.

Highlights

  • Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR)

  • The green fluorescent protein (GFP)or ZsGreen-positive cells were sorted by fluorescence-activated cell sorting (FACS; Supplementary Fig. 1a) and enrichment of Trace amine-associated receptors (TAARs) OSNs was verified by RNA-seq

  • The GFP- or ZsGreennegative cells were sorted to serve as control cells, approximately 70–80% of which are composed of OR-expressing OSNs

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Summary

Introduction

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations Both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We show that the TAAR enhancers operate in cis to regulate Taar gene expression. OSNs expressing different olfactory receptor gene families constitute distinct olfactory subsystems that detect specific categories of odorants. While the OR enhancers interact in trans to form the multi-enhancer hub, their restricted effects on proximal OR gene expression suggest that they operate in cis. Taar genes are arranged in a single cluster in chromosome 10 and are numbered based on their chromosomal order, from Taar[1] to Taar[9], with five intact Taar[7] genes

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