Cell Biology

Smell of Genes Packed Away

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Science  07 Dec 2012:
Vol. 338, Issue 6112, pp. 1265
DOI: 10.1126/science.338.6112.1265-b

To allow responses to specific odorants, mammalian olfactory sensory neurons form clusters that express just 1 of almost 3000 olfactory receptor alleles. Clowney et al. explored the mechanism by which the promoters of all the rest of these genes are maintained in an inactive state. In mouse olfactory sensory neurons, the unused promoters were spatially organized in about five large foci from which the active gene was excluded. Unlike most cells, where inactive heterochromatin is localized to the periphery of the nucleus, the olfactory receptor genes were located near the center of the nuclei. This “inside-out” morphology is similar to that observed in mice lacking functional lamin b receptor, a protein of the nuclear envelope that interacts with lamins and heterochromatin. Indeed, lamin b receptor was down-regulated during sensory neuron differentiation. Forced expression of the lamin b receptor reversed the morphological sequestration of the olfactory receptor genes and also decreased the expression of the chosen active allele, probably because the thousands of transcription factor binding sites of the normally sequestered olfactory receptor genes were now competing for binding of activating factors. Thus, spatial organization in the nucleus appears to have an essential role in control of this extreme example of monoallelic gene expression.

Cell 151, 724 (2012).

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