Monoallelic Expression of Olfactory Receptors

Abstract

The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron’s odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture.

Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo

“…In that regard, separating compacted from non-compacted chromatin fibers (Bantignies et al, 2011; Clowney et al, 2012; Markenscoff-Papadimitriou et al, 2014) could be a more urgent task for the maintenance of a cell-type specific expression program than the convergence of co-regulated loci. In this regard, interchromosomal association of co-regulated loci (Clowney et al, 2012; Markenscoff-Papadimitriou et al, 2014) due to its stochastic nature may be suitable only for biological systems that tolerate, or even seek, stochasticity like the olfactory and the immune systems (Dekker and Mirny, 2016; Monahan and Lomvardas, 2015; Proudhon et al, 2015; Raviram et al, 2016). Nevertheless, non-stereotypic convergence of multiple gene loci (Osborne et al, 2007) and regulatory sequences in transcription factories (Li et al, 2012a) may also contribute to their co-regulation and their transcription at similar rates at a cellular population level.…”

The 3D Genome as Moderator of Chromosomal Communication

“…Regulation of olfactory receptor genes in neurons represents an interesting example of this, as proposed and carefully documented by the Lomvardas laboratory (Lomvardas et al, 2006; Markenscoff-Papadimitriou et al, 2014; Monahan and Lomvardas, 2015). Olfactory neurons contain several thousand olfactory receptor genes but each neuron expresses only one of these, and different neurons express different receptors.…”

Spatial genome organization and cognition

“…For example, a subtype among the olfactory receptor gene family, the trace amine-associated receptors, undergo mono-allelic dissociation from lamin proteins and the nuclear periphery during the course of olfactory sensory neuron differentiation 32 . Early studies suggest that by relocating to inner compartments of the nucleus, olfactory receptor genes could encounter localized accumulations of transcription factors and an open chromatin environment that facilitates promoter-enhancer interactions and gene expression 32, 33 .…”