Decoding the Mechanisms of Olfactory Receptor Selection in Mammalian Nose

Researchers have discovered that olfactory sensory neurons (OSNs) use RNA-mediated symmetry breaking to achieve singular olfactory receptor (OR) choice. OSNs stably express one OR from over 1,000 available genes in a monogenic and monoallelic fashion. The expression of ORs in mature OSNs requires genomic interactions between the active OR allele and a network of OR gene-specific enhancers called Greek islands (GIs). Through single-nucleus ATAC-seq and RNA-seq, the researchers found that GI accessibility gradually increases during neuronal differentiation and then declines sharply during the transition to mature OSNs. They also observed distinct features between active and inactive GI hubs, including differences in contact specificity, biochemical properties, and histone modification patterns. These findings provide insights into the regulatory mechanisms underlying singular OR transcription in OSNs.