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High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity
Published on: June 2, 2014
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LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice.
Kevin Monahan1, Adan Horta2, Stavros Lomvardas3,4,5
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Nature
|January 11, 2019
Summary
Mouse olfactory sensory neurons exhibit unique genome organization. Specific interchromosomal contacts link olfactory receptor genes across chromosomes, orchestrated by
Area of Science:
- Genomics
- Molecular Biology
- Cell Biology
Background:
- The genome is organized into topologically associated domains and genomic compartments.
- DNA structure typically limits interactions between genes on different chromosomes.
Purpose of the Study:
- To investigate nuclear organization in mouse olfactory sensory neurons.
- To identify mechanisms of olfactory receptor gene regulation.
Main Methods:
- Chromatin conformation capture using in situ Hi-C.
- Fluorescence-activated cell sorting of olfactory sensory neurons and progenitors.
Main Results:
- Olfactory receptor gene clusters from 18 chromosomes form specific interchromosomal contacts.
- These contacts increase with cell differentiation and are mediated by 'Greek island' enhancers.
- A multi-chromosomal super-enhancer forms and associates with the active olfactory receptor gene.
Conclusions:
- Mouse olfactory sensory neurons display a unique nuclear architecture with trans interactions.
- Intergenic enhancers ('Greek islands') and transcription factors (LHX2, LDB1) orchestrate olfactory receptor gene expression through these contacts.
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