Nuclear aggregation of olfactory receptor genes governs their monogenic expression

Cell. 2012 Nov 9;151(4):724-737. doi: 10.1016/j.cell.2012.09.043.

Abstract

Gene positioning and regulation of nuclear architecture are thought to influence gene expression. Here, we show that, in mouse olfactory neurons, silent olfactory receptor (OR) genes from different chromosomes converge in a small number of heterochromatic foci. These foci are OR exclusive and form in a cell-type-specific and differentiation-dependent manner. The aggregation of OR genes is developmentally synchronous with the downregulation of lamin b receptor (LBR) and can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR-induced reorganization of nuclear architecture and disruption of OR aggregates perturbs the singularity of OR transcription and disrupts the targeting specificity of the olfactory neurons. Our observations propose spatial sequestering of heterochromatinized OR family members as a basis of monogenic and monoallelic gene expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / chemistry*
  • Cell Nucleus / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Down-Regulation
  • Gene Expression Regulation
  • Heterochromatin / metabolism
  • In Situ Hybridization, Fluorescence
  • Lamin B Receptor
  • Mice
  • Olfactory Receptor Neurons / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Odorant / genetics*
  • Transcription, Genetic

Substances

  • Cbx1 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Odorant

Associated data

  • GEO/GSE38488