Olfactory receptor choice: a case study for gene regulation in a multi-enhancer system

The mammalian genome possesses >2000 olfactory receptor (OR) alleles regulated by 63 known OR-Enhancer elements, yet each olfactory sensory neuron (OSN) expresses only a single OR allele. Choreographed changes to OSN nuclear architecture are evidently necessary for OR expression. Additionally, the insulated organization of OR-enhancers around an OR allele is a hallmark of the chosen OR. However, the biology guiding OR choice itself is unclear. Innovations in single-cell and biophysics-based analysis of nuclear architecture are revising previous models of the nucleus to include its dynamic and probabilistic nature. In this review, we ground current knowledge of OR gene regulation in these emerging theories to speculate on mechanisms that may give rise to diverse and singular OR expression.