Edited by Linda B. Buck, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved January 9, 2014 (received for review September 10, 2013)
The mechanisms underlying odorant receptor (OR) monoallelic and monogenic expression are unclear. We show for the first time that the nuclei of olfactory neurons have a characteristic organization of facultative heterochromatin: it is highly concentrated around a large constitutive heterochromatin block located centrally in the nucleus. In addition, we show that the homologous alleles of a given OR gene are located in different chromatin compartments in the olfactory nucleus: while one of the alleles is associated with deeply repressed constitutive heterochromatin, the other one is located in or close to the more plastic facultative heterochromatin. This spatial organization is likely to be important for both the monoallelic and monogenic expression of these genes.
Odorants are detected by odorant receptors, which are located on olfactory sensory neurons of the nose. Each olfactory sensory neuron expresses one single odorant receptor gene allele from a large family of odorant receptor genes. To gain insight into the mechanisms underlying this monogenic and monoallelic expression, we examined the 3D nuclear organization of olfactory sensory neurons and determined the positions of homologous odorant receptor gene alleles in relation to different nuclear compartments. Our results show that olfactory neurons exhibit a singular nuclear architecture that is characterized by a large centrally localized constitutive heterochromatin block and by the presence of prominent facultative heterochromatin domains that are localized around this constitutive heterochromatin block. We also found that the two homologous alleles of a given odorant receptor gene are frequently segregated to separate compartments in the nucleus, with one of the alleles localized to the constitutive heterochromatin block and the other one localized to the more plastic facultative heterochromatin, or next to it. Our findings suggest that this nuclear compartmentalization may play a critical role in the expression of odorant receptor genes.
Author contributions: L.M.A.-C. and B.M. designed research; L.M.A.-C., L.M.G., and D.Y.C.B. performed research; L.M.A.-C. and B.M. analyzed data; and B.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1317036111/-/DCSupplemental.
