Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation

Mélanie A Eckersley-Maslin,David Thybert,Jan H Bergmann,John C Marioni,Paul Flicek,David L Spector

doi:10.1016/j.devcel.2014.01.017

Mélanie A Eckersley-Maslin, David Thybert + Show 4 more

Open Access

https://doi.org/10.1016/j.devcel.2014.01.017

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Abstract

Random autosomal monoallelic gene expression refers to the transcription of a gene from one of two homologous alleles. We assessed the dynamics of monoallelic expression during development through an allele-specific RNA-sequencing screen in clonal populations of hybrid mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We identified 67 and 376 inheritable autosomal random monoallelically expressed genes in ESCs and NPCs, respectively, a 5.6-fold increase upon differentiation. Although DNA methylation and nuclear positioning did not distinguish the active and inactive alleles, specific histone modifications were differentially enriched between the two alleles. Interestingly, expression levels of 8% of the monoallelically expressed genes remained similar between monoallelic and biallelic clones. These results support a model in which random monoallelic expression occurs stochastically during differentiation and, for some genes, is compensated for by the cell to maintain the required transcriptional output of these genes.

Highlights

The majority of gene expression in diploid cells is carried out through expression of both alleles of each gene
Random autosomal monoallelic gene expression refers to the transcription of a gene from one of two homologous alleles
We assessed the dynamics of monoallelic expression during development through an allele-specific RNA-sequencing screen in clonal populations of hybrid mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs)

Summary

Introduction

The majority of gene expression in diploid cells is carried out through expression of both alleles of each gene. Several interesting cases of monoallelic expression, in which there is transcription from only one allele, have been documented. Random monoallelic expression can occur on autosomes independently of parental origin and genotype (reviewed in Chess, 2012; Guo and Birchler, 1994). Neurons express olfactory receptors (ORs) in a monogenic and monoallelic manner to provide cell identity and aid in neural connectivity (Chess et al, 1994). Random autosomal monoallelic expression is not limited to specialized gene families, as it has been reported to occur at individual gene loci throughout the genome of a few cell types examined (Gimelbrant et al, 2007; Jeffries et al, 2012; Li et al, 2012; Zwemer et al, 2012). Despite the identification of such genes, detailed molecular characterization and potential biological consequences of random monoallelic expression remain unknown

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