title: Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments.
abstract: 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 combinatorial manner to encode the unique identities of myriad 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 in Taar gene 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 of Olfr (OR) and Taar expression in different OSNs: the sequestration of Olfr and Taar genes in different nuclear compartments. Although most Olfr genes colocalize near large central heterochromatin aggregates in the OSN nucleus, Taar genes are located primarily at the nuclear periphery, coincident with a thin rim of heterochromatin. Taar-expressing OSNs show a shift of one Taar allele away from the nuclear periphery. Furthermore, examination of hemizygous mice with a single Taar allele 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.
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
authors.forename: Kyoung-Hye
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ragoczy
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
authors.forename: Kunio
authors.initials: K
authors.lastname: Kondoh
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
authors.forename: Donghui
authors.initials: D
authors.lastname: Kuang
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Mark
authors.initials: M
authors.lastname: Groudine
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and lbuck@fhcrc.org.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Buck
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism*; D022202:Chromosomes, Artificial, Bacterial; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000378:metabolism; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D034904:Lamin Type A / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009812:Odorants; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000502:physiology; D018035:Receptors, Odorant / Q000235:genetics*; D011984:Sensory Receptor Cells / Q000378:metabolism; D012903:Smell / Q000502:physiology
chemical_list: D006570:Heterochromatin; D034904:Lamin Type A; D018035:Receptors, Odorant
keywords: Taar genes; nuclear organization; olfactory receptor genes