Stochastic gene expression in mammals: lessons from olfaction

•Stochasticity is important for the regulation of several mammalian gene families.•It is often mediated via epigenetic silencing and nuclear architecture.•Olfactory receptor expression is a prime paradigm of stochastic choice in neurons.•Critical functions of the nervous and immune systems are based on stochastic choices.

One of the remarkable characteristics of higher organisms is the enormous assortment of cell types that emerge from a common genome. The immune system, with the daunting duty of detecting an astounding number of pathogens, and the nervous system with the equally bewildering task of perceiving and interpreting the external world, are the quintessence of cellular diversity. As we began to appreciate decades ago, achieving distinct expression programs among similar cell types cannot be accomplished solely by deterministic regulatory systems, but by the involvement of some type of stochasticity. In the last few years our understanding of these non-deterministic mechanisms is advancing, and this review will provide a brief summary of the current view of stochastic gene expression with focus on olfactory receptor (OR) gene choice, the epigenetic underpinnings of which recently began to emerge.