Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 18; pp. E2403 - E2409
• Main Authors: Yoon, Kyoung-hye, Ragoczy, Tobias, Lu, Zhonghua, Kondoh, Kunio, Kuang, Donghui, Groudine, Mark, Buck, Linda B.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.05.2015; National Acad Sciences
• Series: PNAS Plus
• Subjects: Alleles; Animals; Biological Sciences; Cell Lineage; Cell Nucleus - metabolism; Chemicals; Chemosensory perception; Chromatin; Chromosomes, Artificial, Bacterial; Crosses, Genetic; Female; Gene expression; Gene Expression Regulation; Heterochromatin - metabolism; In Situ Hybridization; In Situ Hybridization, Fluorescence; Lamin Type A - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neurons; Odorants; Odors; Olfactory Mucosa - metabolism; Olfactory Receptor Neurons - physiology; PNAS Plus; Receptors, Odorant - genetics; Sensory Receptor Cells - metabolism; Smell - physiology; Taar genes; olfactory receptor genes; nuclear organization
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1506058112

The olfactory system translates a vast array of volatile chemicals into diverse odor perceptions and innate behaviors. Odor detection in the mouse nose is mediated by 1,000 different odorant receptors (ORs) and 14 trace amine-associated receptors (TAARs). ORs are used in a combinatorialmanner to encode the unique identities ofmyriad odorants. However, some TAARs appear to be linked to innate responses, raising questions about regulatory mechanisms that might segregate OR and TAAR expression in appropriate subsets of olfactory sensory neurons (OSNs). Here, we report that OSNs that express TAARs comprise at least two subsets that are biased to express TAARs rather than ORs. The two subsets are further biased inTaargene choice and their distribution within the sensory epithelium, with each subset preferentially expressing a subgroup of Taar genes within a particular spatial domain in the epithelium. Our studies reveal one mechanism that may regulate the segregation ofOlfr(OR) andTaarexpression in different OSNs: the sequestration ofOlfrandTaargenes in different nuclear compartments. Although mostOlfrgenes colocalize near large central heterochromatin aggregates in the OSN nucleus,Taargenes are located primarily at the nuclear periphery, coincident with a thin rim of heterochromatin.Taar-expressing OSNs show a shift of oneTaarallele away from the nuclear periphery. Furthermore, examination of hemizygous mice with a singleTaarallele suggests that the activation of a Taar gene is accompanied by an escape from the peripheral repressive heterochromatin environment to a more permissive interior chromatin environment.