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Allelic inactivation regulates olfactory receptor gene expression
1Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Cell
|September 9, 1994
Summary
A new model explains how single sensory neurons express only one odorant receptor gene from a large family. This ensures precise odor detection by controlling gene expression at the DNA level.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Sensory neurons detect odors by expressing specific odorant receptor (OR) proteins.
- A single neuron typically expresses only one type of OR from a large family of genes (around 1000 in mammals).
- The precise mechanism ensuring this single-gene expression remains incompletely understood.
Purpose of the Study:
- To propose and support a model explaining the molecular mechanisms of single odorant receptor gene expression in sensory neurons.
- To elucidate how a neuron selects and expresses a single functional OR gene from a vast repertoire.
Main Methods:
- The study proposes a model based on existing genetic and molecular biology principles.
- It integrates observations on cis-regulatory elements, stochastic gene expression, allelic exclusion, and asynchronous DNA replication.
- The model infers mechanisms from the observed patterns of gene expression and allele activity.
Main Results:
- A hierarchy of controls regulates the expression of odorant receptor genes.
- A cis-regulatory element is proposed to direct stochastic expression of a single gene from a linked array.
- Expression is restricted to one allele, with asynchronous replication linked to allelic inactivation.
Conclusions:
- The proposed model explains how individual sensory neurons achieve monoallelic and monospecific odorant receptor expression.
- This mechanism involves cis-regulatory control over a single active allelic array and inactivation of the other.
- This ensures reliable and specific odor detection by individual neurons.
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