Cell
Volume 151, Issue 4, 9 November 2012, Pages 724-737
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Article
Nuclear Aggregation of Olfactory Receptor Genes Governs Their Monogenic Expression

https://doi.org/10.1016/j.cell.2012.09.043Get rights and content
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Summary

Gene positioning and regulation of nuclear architecture are thought to influence gene expression. Here, we show that, in mouse olfactory neurons, silent olfactory receptor (OR) genes from different chromosomes converge in a small number of heterochromatic foci. These foci are OR exclusive and form in a cell-type-specific and differentiation-dependent manner. The aggregation of OR genes is developmentally synchronous with the downregulation of lamin b receptor (LBR) and can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR-induced reorganization of nuclear architecture and disruption of OR aggregates perturbs the singularity of OR transcription and disrupts the targeting specificity of the olfactory neurons. Our observations propose spatial sequestering of heterochromatinized OR family members as a basis of monogenic and monoallelic gene expression.

Highlights

► In olfactory neurons, OR genes converge in specialized heterochromatic foci ► The active OR allele in each neuron is transcribed outside of these foci ► Lamin B receptor (LBR) downregulation allows OR aggregation in olfactory neurons ► Ectopic LBR expression disrupts OR foci and causes OR coexpression

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