Stochastic fluctuations and distributed control of gene expression impact cellular memory

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 do...

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Bibliographic Details
Published in:PloS one 2014-12, Vol.9 (12), p.e115574-e115574
Main Authors: Corre, Guillaume, Stockholm, Daniel, Arnaud, Ophélie, Kaneko, Gaël, Viñuelas, José, Yamagata, Yoshiaki, Neildez-Nguyen, Thi My Anh, Kupiec, Jean-Jacques, Beslon, Guillaume, Gandrillon, Olivier, Paldi, András
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Biology and Life Sciences
Biotechnology
Cell cycle
Cell division
Cell Lineage - genetics
Cellular Biology
Computer memory
Computer Simulation
Conservation
Development Biology
Dynamic tests
Embryo, Mammalian - metabolism
Embryo, Mammalian - pathology
Epigenetics
Epigenomics
Fluorescence
Gene expression
Gene Expression Regulation, Neoplastic
Genes, Reporter
Genetics
Genomics
Heterogeneity
Humans
Life Sciences
Mammals
Mathematical models
Molecular biology
mRNA stability
mRNA turnover
Noise
Phenotype
Population
Proteins
Quantitative Methods
Reporter gene
Retinoblastoma - genetics
Retinoblastoma - pathology
Stochastic Processes
Stochasticity
Transcription, Genetic
Transgenes
Tumor Cells, Cultured
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0115574