title: Developmental dynamics and disease potential of random monoallelic gene expression.
abstract: X chromosome inactivation (XCI) and allelic exclusion of olfactory receptors or immunoglobulin loci represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation, and, once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism. Several of the RME genes identified play important roles in development and have been implicated in human autosomal-dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control, and, in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease.
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France.
authors.forename: Anne-Valerie
authors.initials: AV
authors.lastname: Gendrel
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Attia
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, Paris 75248, France; Mines ParisTech, Fontainebleau 77300, France.
authors.forename: Chong-Jian
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Diabangouaya
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, Paris 75248, France; Mines ParisTech, Fontainebleau 77300, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, Paris 75248, France; Mines ParisTech, Fontainebleau 77300, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.affiliation: Institut Curie, 26 rue d'Ulm, Paris 75248, France; Genetics and Developmental Biology Unit, INSERM U934/CNRS UMR3215, Paris 75248, France. Electronic address: edith.heard@curie.fr.
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D019175:DNA Methylation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D049951:X Chromosome Inactivation