title: Random monoallelic gene expression increases upon embryonic stem cell differentiation.
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.
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Mélanie A
authors.initials: MA
authors.lastname: Eckersley-Maslin
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Thybert
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Bergmann
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Marioni
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA; Watson School of Biological Sciences, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: spector@cshl.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Spector
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002875:Chromosomes / Q000235:genetics; D019175:DNA Methylation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D017423:Sequence Analysis, RNA / Q000379:methods