Quantifying the contribution of chromatin dynamics to stochastic gene expression reveals long, locus-dependent periods between transcriptional bursts.

José Viñuelas 1 Gaël Kaneko 1, 2, 3 Antoine Coulon 4 Elodie Vallin 1 Valérie Morin 1 Camila Mejia-Pous 1 Jean-Jacques Kupiec 5 Guillaume Beslon 2, 3 Olivier Gandrillon 1, *
* Auteur correspondant
3 BEAGLE - Artificial Evolution and Computational Biology
LIRIS - Laboratoire d'InfoRmatique en Image et Systèmes d'information, Inria Grenoble - Rhône-Alpes, LBBE - Laboratoire de Biométrie et Biologie Evolutive, CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
5 Centre Cavaillès
La République des savoirs : Lettres, Sciences, Philosophie
Abstract : ABSTRACT: BACKGROUND: A number of studies have established that stochasticity in gene expression may play an important role in many biological phenomena. This therefore calls for further investigations to identify the molecular mechanisms at stake, in order to understand and manipulate cell-to-cell variability. In this work, we explored the role played by chromatin dynamics in the regulation of stochastic gene expression in higher eukaryotic cells. RESULTS: For this purpose, we 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 showed that direct manipulation of chromatin dynamics had a marked effect on the extent of stochastic gene expression. To better understand the molecular mechanism involved in these phenomena, we fitted these data to a two-state model describing the opening/closing process of the chromatin. We found 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. CONCLUSIONS: In this study, we report biological experiments combined with computational modeling, highlighting the importance of chromatin dynamics in stochastic gene expression. This work sheds 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.
Type de document :
Article dans une revue
BMC Biology, BioMed Central, 2013, 11 (1), pp.15. 〈10.1186/1741-7007-11-15〉
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Soumis le : jeudi 25 avril 2013 - 17:06:47
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José Viñuelas, Gaël Kaneko, Antoine Coulon, Elodie Vallin, Valérie Morin, et al.. Quantifying the contribution of chromatin dynamics to stochastic gene expression reveals long, locus-dependent periods between transcriptional bursts.. BMC Biology, BioMed Central, 2013, 11 (1), pp.15. 〈10.1186/1741-7007-11-15〉. 〈inserm-00817963〉



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