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Thursday
Apr212016

Epigenetics and our sense of smell

The olfactory sensory neurons (OSNs) are a unique population of neurons that allow us to detect and identify specific odorants. The odorants are detected when they bind to specific olfactory receptors (ORs) expressed by the OSNs. Once an odorant is bound, a signaling cascade is initiated to notify neurons in the adjacent olfactory bulb and the rest of the olfactory pathway that the odorant is present.  

Usually, OSNs express a single olfactory receptor, and the axons of all OSNs that express the same OR meet at the same location within the olfactory bulb. It’s a great system – all inputs for a particular odor meet up in the same region of the olfactory bulb, presumably to consolidate and simplify the odor signals received by the brain.

But this system is also complex. It relies on each and every OSN expressing a single OR. In mice, this requires a selection of one OR out of a possible 1,400. Once chosen, the OR selection needs to be maintained throughout the life of the neuron, or bananas might start to smell like garbage.

On the surface, it makes sense that epigenetic regulation would be involved in the OR selection process – as one gene must be expressed in the face of a multitude of options. But how does this actually happen?

A recent study by Lyons, DB et al (1), used an army of mouse models to parse out important protein expression patterns necessary for the installment of a single OR in a single OSN. To begin, they found that the epigenetic protein lysine-specific demethylase 1 (LSD1) is involved in de-silencing individual ORs through histone H3 lysine K9 (H3K9) demethylase activity.  This initial process allows the next step to occur, transcriptional activation through histone H3 lysine K4 (H3K4) trimethylation, which initiates production of the OR.

So how is the selective expression of a single OR maintained? This is achieved through induction of adenylate cyclase 3 expression by the OR. Adenylate cyclase 3 expression downregulates LSD1 expression, and prevents the transcriptional activation of other ORs. Thus, once Adenylate cyclase 3 is expressed, the neuron becomes “trapped” through a feedback loop into making a single OR. And there you have it – bananas continue to smell like bananas.

 ~GV

1)     Lyons DB, Allen WE, Goh T, Tsai L, Barnea G, Lomvardas S. An epigenetic trap stabilizes singular olfactory receptor expression. Cell, 2013, 154, 325-336.

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