Stochastic fluctuations and distributed control of gene expression impact cellular memory

PLoS One. 2014 Dec 22;9(12):e115574. doi: 10.1371/journal.pone.0115574. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Lineage / genetics*
  • Computer Simulation
  • Embryo, Mammalian / metabolism*
  • Embryo, Mammalian / pathology*
  • Epigenomics
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Phenotype
  • Retinoblastoma / genetics*
  • Retinoblastoma / pathology*
  • Stochastic Processes*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Grant support

Agence National de Recherche, grant Stochagene grant no. BSV6 014 02, Genethon. Equipment funds were from Genopole Research-Evry, University Evry Val d'Essonne, Conseil General de l'Essonne and from Region Ile de France. GC was a recipient of an AXA PhD fellowship. YY was financed by Department of Obstetrics and Gynaecology, Yamaguchi University Graduate School of Medicine, Ube, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.