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Interchromosomal interactions and olfactory receptor choice.

Stavros Lomvardas1, Gilad Barnea, David J Pisapia

  • 1Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

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Summary
This summary is machine-generated.

A single enhancer element (H) on chromosome 14 associates with olfactory receptor (OR) gene promoters. This enhancer may control the stochastic activation of only one OR gene in sensory neurons.

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Area of Science:

  • Olfactory system biology
  • Genetics and genomics
  • Molecular mechanisms of gene regulation

Background:

  • Olfactory receptor (OR) gene expression in individual sensory neurons is crucial for olfactory system organization and function.
  • ORs form a large gene family, and typically only one OR gene is expressed per neuron.
  • Understanding the regulatory mechanisms governing single OR gene expression is key to olfactory research.

Purpose of the Study:

  • To investigate the role of enhancer elements in the regulation of olfactory receptor gene expression.
  • To determine how a specific enhancer element (H) interacts with OR gene promoters.
  • To elucidate the mechanism controlling the choice of a single OR gene for expression in olfactory sensory neurons.

Main Methods:

  • Chromosome conformation capture (3C) was employed to identify interactions between enhancer elements and OR gene promoters.
  • DNA and RNA fluorescence in situ hybridization (FISH) were used to visualize the physical association and transcriptional status of enhancer-promoter interactions.
  • Transgenic mouse models were created to study the effects of additional enhancer elements on OR expression.

Main Results:

  • The H enhancer element on chromosome 14 was shown to specifically associate with OR gene promoters located on different chromosomes.
  • FISH experiments confirmed the colocalization of the H enhancer with the single actively transcribed OR allele in sensory neurons.
  • Transgenic mice with extra H elements exhibited expression of a second functional receptor in neurons that normally express OR pseudogenes.

Conclusions:

  • A single trans-acting enhancer element (H) can mediate the specific association with multiple OR gene promoters.
  • The H enhancer plays a critical role in the stochastic activation of a single OR allele in olfactory sensory neurons.
  • These findings propose a model where a single enhancer regulates olfactory receptor gene choice.