Epigenetic gene expression noise and phenotypic diversification of clonal cell populations.
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.
Neildez-Nguyen
Thi My Anh
TM
GENETHON, Centre National de la Recherche Scientifique UMR 8115 1 bis, rue de l'Internationale, 91002 Evry, France.
Parisot
Aurélie
A
Vignal
Céline
C
Rameau
Philippe
P
Stockholm
Daniel
D
Picot
Julien
J
Allo
Valérie
V
Le Bec
Christine
C
Laplace
Corinne
C
Paldi
Andras
A
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