title: Epigenetic gene expression noise and phenotypic diversification of clonal cell populations.
abstract: Spontaneous emergence of phenotypic heterogeneity in cultures of genetically identical cells is a frequently observed phenomenon that provides a simple in vitro experimental system to model the problems of in vivo differentiation. In the present study, we have investigated whether stochastic variation of gene expression levels could contribute to phenotypic change in human cells. We have applied the two fluorescence-coding gene method and the expression variability of the two reporter genes to human cells in culture. We have quantified the portion of gene expression variation determined by global, promoter-specific, or by epigenetic sources. These two types of variation appear to contribute, in different ways, to the phenotypic diversification of clonal cell populations. Global, or promoter-specific, gene expression noise increases with cellular stress and contributes to the emergence of cellular diversity by diversifying the gene-expression levels. Epigenetic mechanisms act to increase the robustness of the cellular state by stabilizing gene transcription levels or by reinforcing the silenced state.
authors.affiliation: GENETHON, Centre National de la Recherche Scientifique UMR 8115 1 bis, rue de l'Internationale, 91002 Evry, France.
authors.forename: Thi My Anh
authors.initials: TM
authors.lastname: Neildez-Nguyen
authors.forename: Aurélie
authors.initials: A
authors.lastname: Parisot
authors.forename: Céline
authors.initials: C
authors.lastname: Vignal
authors.forename: Philippe
authors.initials: P
authors.lastname: Rameau
authors.forename: Daniel
authors.initials: D
authors.lastname: Stockholm
authors.forename: Julien
authors.initials: J
authors.lastname: Picot
authors.forename: Valérie
authors.initials: V
authors.lastname: Allo
authors.forename: Christine
authors.initials: C
authors.lastname: Le Bec
authors.forename: Corinne
authors.initials: C
authors.lastname: Laplace
authors.forename: Andras
authors.initials: A
authors.lastname: Paldi
mesh_terms: D045744:Cell Line, Tumor / Q000166:cytology / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics; D002999:Clone Cells / Q000166:cytology / Q000502:physiology*; D054278:Embryonal Carcinoma Stem Cells; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D023061:Gene Order; D017930:Genes, Reporter; D018740:Genetic Heterogeneity; D006801:Humans; D016254:Mutagenesis, Insertional; D010641:Phenotype; D013269:Stochastic Processes