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Chromosomes organize to ensure each nose cell expresses only one smell receptor

house mouse/George Shuklin (CC BY-SA 1.0)

For the same type of reason, perhaps, as each key only produces one letter (prevents information from being degraded even as it is produced). Researchers have learned that mice use a sort of “high-tech” hub to ensure that only one odor-sensing receptor is expressed in each neuron:

Mammals can discriminate between a vast number of volatile compounds — perhaps more than a trillion1. This extraordinary capacity is encoded by a repertoire of hundreds of olfactory-receptor genes, distributed in small groups that are present on almost all chromosomes2. To ensure that the response to individual odours is specific, each olfactory sensory neuron (OSN) expresses a single, randomly selected olfactory-receptor gene. Writing in Nature, Monahan et al.3 show that, in the nuclei of mouse OSNs, certain regions of multiple chromosomes assemble in a structure that controls the expression of the full repertoire of olfactory-receptor genes in the nose, while making sure that each cell expresses only one type of receptor. These exciting findings show that interchromosomal interactions can have a determinant role in regulating gene expression.François Spitz, “Chromosomes come together to help mice distinguish odours” at Nature

A reader wrote to say, “More evidence that spatial information regulates gene expression.”

The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we report a marked divergence from this pattern of nuclear organization that occurs in mouse olfactory sensory neurons. Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the ‘Greek islands’, which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. Monahan, K., Horta, A. & Lomvardas, S. Nature https://doi.org/10.1038/s41586-018-0845-0 (2019). Abstract: (paywall) More.

See also: 2018 Saw Mechanobiology, Including Biophysics, Come To The Fore

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Great paper, thank you! :)gpuccio
January 18, 2019
03:07 PM

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