4.4 Article

Olfactory receptor choice: a case study for gene regulation in a multi-enhancer system

Journal

CURRENT OPINION IN GENETICS & DEVELOPMENT
Volume 72, Issue -, Pages 101-109

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2021.11.003

Keywords

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Funding

  1. office of the NIH Director 4D Nucleome program [U01DA052783]
  2. NIDCD [R01DC018744]
  3. MSTP [T32GM007367]

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This review examines the current knowledge of olfactory receptor gene regulation and speculates on mechanisms that may contribute to diverse and singular olfactory receptor expression, based on emerging theories of nuclear architecture.
The mammalian genome possesses >2000 olfactory receptor (OR) alleles regulated by 63 known OR-Enhancer elements, yet each olfactory sensory neuron (OSN) expresses only a single OR allele. Choreographed changes to OSN nuclear architecture are evidently necessary for OR expression. Additionally, the insulated organization of OR enhancers around an OR allele is a hallmark of the chosen OR. However, the biology guiding OR choice itself is unclear. Innovations in single-cell and biophysics-based analysis of nuclear architecture are revising previous models of the nucleus to include its dynamic and probabilistic nature. In this review, we ground current knowledge of OR gene regulation in these emerging theories to speculate on mechanisms that may give rise to diverse and singular OR expression.

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