Nuclear compartmentalization of odorant receptor genes

Armelin‐Correa, Lucia; Gutiyama, Luciana M.; Brandt, Débora Y. C.; Malnic, Bettina

doi:10.1073/pnas.1317036111

Cited by 61 publications

(67 citation statements)

References 52 publications

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“…Using Olfr probes, the labeled foci were mostly located within the nucleoplasm and often at or near central chromocenters, as previously reported (Fig. 2 B-E) (24,25). Only one of the five Olfr BACs (155M18) labeled foci Fig.…”

Section: Resultssupporting

confidence: 84%

“…The interior foci are referred to as "chromocenters", because they contain aggregates of DNA and are therefore strongly stained by DAPI (4′,6-diamidino-2-phenylindole dihydrochloride), which binds DNA. However, OSNs have an unusual nuclear architecture in which heterochromatin in the nuclear interior is aggregated at one or a few large chromocenters rather than in multiple smaller chromocenters, as seen in other cell types (24,25). Previous studies indicate that Olfr genes are colocalized at these chromocenters (24,25).…”

Section: Resultsmentioning

confidence: 99%

“…However, OSNs have an unusual nuclear architecture in which heterochromatin in the nuclear interior is aggregated at one or a few large chromocenters rather than in multiple smaller chromocenters, as seen in other cell types (24,25). Previous studies indicate that Olfr genes are colocalized at these chromocenters (24,25). In mutant mice lacking these large foci, Olfr genes do not cluster and are abnormally expressed, leading to the proposal that the aggregation of Olfr genes governs their monogenic expression (24).…”

Section: Resultsmentioning

confidence: 99%

“…At the level of the nucleus, we find a striking difference between the intranuclear compartments containing Taar versus Olfr genes. In sharp contrast to Olfr genes, which reside primarily in the nuclear interior near large heterochromatin aggregates (24,25), Taar genes preferentially localize to a thin rim of heterochromatin adjacent to the nuclear envelope. Our studies further…”

mentioning

confidence: 78%

“…In OSNs, however, heterochromatin is largely concentrated in one or a few large central heterochromatin aggregates. It has been reported that most Olfr genes colocalize in or near these large chromocenters (24,25). Ectopic OSN expression of the lamina binding protein LBR prevents the formation of the large chromocenters and Olfr gene clustering, and causes the misexpression of hundreds of genes, including Olfr genes.…”

Section: Discussionmentioning

confidence: 99%

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

Yoon

Ragoczy

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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. olfactory receptor genes | Taar genes | nuclear organization

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Yoon

Ragoczy

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Epigenetic programming of stochastic olfactory receptor choice

Yusuf,

Monahan

2024

Genesis

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SummaryThe mammalian sense of smell relies upon a vast array of receptor proteins to detect odorant compounds present in the environment. The proper deployment of these receptor proteins in olfactory sensory neurons is orchestrated by a suite of epigenetic processes that remodel the olfactory genes in differentiating neuronal progenitors. The goal of this review is to elucidate the central role of gene regulatory processes acting in neuronal progenitors of olfactory sensory neurons that lead to a singular expression of an odorant receptor in mature olfactory sensory neurons. We begin by describing the principal features of odorant receptor gene expression in mature olfactory sensory neurons. Next, we delineate our current understanding of how these features emerge from multiple gene regulatory mechanisms acting in neuronal progenitors. Finally, we close by discussing the key gaps in our understanding of how these regulatory mechanisms work and how they interact with each other over the course of differentiation.

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Insertion of a neomycin selection cassette in the Amigo1 locus alters gene expression in the olfactory epithelium leading to region‐specific defects in olfactory receptor neuron development

Raja,

Dumontier,

Phen

et al. 2024

Genesis

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SummaryDuring development of the nervous system, neurons connect to one another in a precisely organized manner. Sensory systems provide a good example of this organization, whereby the composition of the outside world is represented in the brain by neuronal maps. Establishing correct patterns of neural circuitry is crucial, as inaccurate map formation can lead to severe disruptions in sensory processing. In rodents, olfactory stimuli modulate a wide variety of behaviors essential for survival. The formation of the olfactory glomerular map is dependent on molecular cues that guide olfactory receptor neuron axons to broad regions of the olfactory bulb and on cell adhesion molecules that promote axonal sorting into specific synaptic units in this structure. Here, we demonstrate that the cell adhesion molecule Amigo1 is expressed in a subpopulation of olfactory receptor neurons, and we investigate its role in the precise targeting of olfactory receptor neuron axons to the olfactory bulb using a genetic loss‐of‐function approach in mice. While ablation of Amigo1 did not lead to alterations in olfactory sensory neuron axonal targeting, our experiments revealed that the presence of a neomycin resistance selection cassette in the Amigo1 locus can lead to off‐target effects that are not due to loss of Amigo1 expression, including unexpected altered gene expression in olfactory receptor neurons and reduced glomerular size in the ventral region of the olfactory bulb. Our results demonstrate that insertion of a neomycin selection cassette into the mouse genome can have specific deleterious effects on the development of the olfactory system and highlight the importance of removing antibiotic resistance cassettes from genetic loss‐of‐function mouse models when studying olfactory system development.

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Nuclear compartmentalization of odorant receptor genes

Cited by 61 publications

References 52 publications

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

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

Epigenetic programming of stochastic olfactory receptor choice

Insertion of a neomycin selection cassette in the Amigo1 locus alters gene expression in the olfactory epithelium leading to region‐specific defects in olfactory receptor neuron development

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