Section: New Results

Stochastic dynamics of gene expression

A number of studies have established that stochasticity in gene expression may play an important role in many biological phenomena but the molecular mechanisms at stake are still poorly understood. By joint experimental and computational approaches, we explored the role played by chromatin dynamics in the regulation of stochastic gene expression in higher eukaryotic cells [31] . For this purpose, our biological partner generated isogenic chicken-cell populations expressing a fluorescent reporter integrated in one copy per clone. Although the clones differed only in the genetic locus at which the reporter was inserted, they showed markedly different fluorescence distributions, revealing different levels of stochastic gene expression. Use of chromatin-modifying agents then showed that direct manipulation of chromatin dynamics had a marked effect on the extent of stochastic gene expression. We then fitted the experimental data to a two-state model describing the opening/closing process of the chromatin. The model showed that the differences between clones seemed to be due mainly to the duration of the closed state, and that the agents we used mainly seem to act on the opening probability. These results highlight the importance of chromatin dynamics in stochastic gene expression. They shed a new light on the mechanisms of gene expression in higher eukaryotic cells, and argues in favor of relatively slow dynamics with long (hours to days) periods of quiet state.

This work was part of Gaël Kaneko's PhD and results from our long-lasting collaboration with Olivier Grandrillon and his BM2A team in the CGphyMC (Centre de Génétique et de Physiologie Moléculaire et Cellulaire, Lyon).