title: Stochastic fluctuations and distributed control of gene expression impact cellular memory.
abstract: Despite the stochastic noise that characterizes all cellular processes the cells are able to maintain and transmit to their daughter cells the stable level of gene expression. In order to better understand this phenomenon, we investigated the temporal dynamics of gene expression variation using a double reporter gene model. We compared cell clones with transgenes coding for highly stable mRNA and fluorescent proteins with clones expressing destabilized mRNA-s and proteins. Both types of clones displayed strong heterogeneity of reporter gene expression levels. However, cells expressing stable gene products produced daughter cells with similar level of reporter proteins, while in cell clones with short mRNA and protein half-lives the epigenetic memory of the gene expression level was completely suppressed. Computer simulations also confirmed the role of mRNA and protein stability in the conservation of constant gene expression levels over several cell generations. These data indicate that the conservation of a stable phenotype in a cellular lineage may largely depend on the slow turnover of mRNA-s and proteins.
authors.affiliation: Inserm, UMR 951, Université d'Evry Val d'Essonne, Genethon, Evry, F91002 France; Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Corre
authors.affiliation: Inserm, UMR 951, Université d'Evry Val d'Essonne, Genethon, Evry, F91002 France; Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stockholm
authors.affiliation: Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGPhiMC), CNRS UMR5534, F-69622 Lyon, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Arnaud
authors.affiliation: Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGPhiMC), CNRS UMR5534, F-69622 Lyon, France; Université de Lyon, INSA-Lyon, INRIA, Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), CNRS UMR5205, F-69621 Lyon, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Kaneko
authors.affiliation: Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGPhiMC), CNRS UMR5534, F-69622 Lyon, France.
authors.forename: José
authors.initials: J
authors.lastname: Viñuelas
authors.affiliation: Department of Obstetrics and Gynaecology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamagata
authors.affiliation: Inserm, UMR 951, Université d'Evry Val d'Essonne, Genethon, Evry, F91002 France; Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: Thi My Anh
authors.initials: TM
authors.lastname: Neildez-Nguyen
authors.affiliation: Centre Cavailles, Ecole Normale Supérieure, 29 rue d'Ulm, 75005 Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kupiec
authors.affiliation: Université de Lyon, INSA-Lyon, INRIA, Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), CNRS UMR5205, F-69621 Lyon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Beslon
authors.affiliation: Université de Lyon, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire (CGPhiMC), CNRS UMR5534, F-69622 Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gandrillon
authors.affiliation: Inserm, UMR 951, Université d'Evry Val d'Essonne, Genethon, Evry, F91002 France; Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: András
authors.initials: A
authors.lastname: Paldi
mesh_terms: D019070:Cell Lineage / Q000235:genetics*; D003198:Computer Simulation; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology*; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D010641:Phenotype; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology*; D013269:Stochastic Processes; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured