Dissecting the physical parameters governing chromosome fluctuations in living cells

The organization of the genome remains the subject of intense research due to its fundamental role in gene expression, DNA replication and genome stability. In the yeast S. Cerevisiae, detailed understanding of the molecular determinants of chromosome folding emerge from combined imaging and molecular biology studies (1,2), but the parameters that govern their dynamics remain more elusive. Using high speed live cell microscopy, we recently showed that the Rouse model, in which chromosome dynamics is described with a series of beads connected by elastic springs, was in reasonable agreement with experimental data of chromosome motion over a broad temporal scale (3). We now focus on technologies for capturing chromosome spatial and temporal fluctuations based on the realization that chromatin conformation is highly dynamic at every length and time scale. We work on the determination of the molecular parameters governing chromosome dynamics, especially the flexibility of the chromatin fiber and its viscous properties. More specifically we investigate the interplay between DNA transcription and chromosome dynamics in order to understand how chromosome folding and nuclear organization are influenced by cellular processes. This research is associated to efforts in physics in order to contribute to a better understanding of the physical properties and mechanisms of chromosome conformation.

References:

1.            Duan et al., Nature 465, 363 (2010).

2.            Albert et al., J Cell Biol 202, 201 (2013).

3.            Hajjoul et al., Genome Research 23, 1829 (2013).

Figure: Live cell imaging of living yeast allows for the detection of the nucleolus, one chromosome locus, and the nuclear periphery, which appear as a red region, a green spot, and a green rim in the right panel, respectively. The analysis of spatial fluctuations defines an architectural model of the yeast based on polymer physics, as represented in the left panel.