Random monoallelic expression: regulating gene expression one allele at a time

Abstract

Monoallelic gene expression is a remarkable process in which transcription occurs from only one of two homologous alleles in a diploid cell. Interestingly, between 0.5% and 15% of autosomal genes exhibit random monoallelic gene expression, in which different cells express only one allele independently of the underlying genomic sequence, in a cell type-specific manner. Recently, genome-wide studies have increased our understanding of the cell type-specific incidence of random monoallelic gene expression, and how the imbalance in allelic expression is distinguished within the cell and potentially maintained across cell generations. Monoallelic gene expression is likely generated through stochastic independent regulation of the two alleles upon differentiation, and has varied implications for the cell and organism, in particular with respect to disease.

Keywords: monoallelic expression; stochastic gene regulation.

Figure 1

Combined RNA (green) and DNA (red) Fluorescence In situ Hybridization (FISH) demonstrating monoallelic expression of Cap2 at the single cell level in mouse neural progenitor cells. DAPI staining is shown in blue. Images represent deconvolved maximum intensity projections, arrows show active allele, arrowheads inactive allele. Scale bar represents 5μm. Image by M. A. Eckersley-Maslin and D. L. Spector, Cold Spring Harbor Laboratory.

Figure 2

Model of stochastic gene regulation generating random monoallelic expression. Gene regulation involves the recruitment of a large array of protein complexes including, but not limited to, histone modifiers, chromatin remodelers, transcription factors and RNA polymerase. For genes that have a low probability of each allele being independently regulated, the resulting population will contain cells with 0 (no expression), 1 (monoallelic expression) or 2 (biallelic expression) active alleles. These states may be propagated through the cell cycle, and, if not detrimental, could have diverse consequences for the cell.