Biophysical investigation of chromosome folding and dynamics

Chromosomes direct the compaction of long DNA fragments in the nucleus of eukaryotic cells. The rules that govern the folding of chromosomes are progressively uncovered owing to the development of modern high-throughput genome-wide molecular biology techniques. These findings are obtained by cross-disciplinary researches involving physics, statistics, and biology, and they shed new light on the mechanisms of gene regulation and genome maintenance. 
In addition to biochemical interactions involving e.g. proteins, which are mapped with a spatial resolution sometimes nearing the base-pair level, the role of biophysical mechanisms in the organization of chromosomes has been increasingly acknowledged. The polymeric nature of chromosomes (that is, their composition in repetitive structural units) has in particular led to structural predictions that follow universal rules independent of the local chemical composition of chromosomes. The physical principles associated to the motion of chromosomes have remained sparsely studied, and research team from Toulouse (LAAS and LBME) and Paris (LPTMC) set out to test the predictions of polymer physics to recapitulate chromosome spatial dynamics. Using innovative high-throughput microscopy techniques, the movements of chromosomes were investigated in different chromosomes of the bakers’ yeast. The folding and the spatial fluctuations appeared to consistent with physical models of polymers. In addition the analysis of the amplitude of spatial fluctuations indicated that yeast chromatin was highly flexible, in fact much more flexible than the DNA itself. This result sheds new light on the dynamics of chromosomes, and has profound implications for yeast genome architecture and for target search mechanisms in the nucleus.

Figure above : 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. 

Références : 
1- Albert B, Mathon J, Shukla A, Saad H, Normand C, Villa D, Kamgoue A, Mozziconacci J, Wong H, Zimmer C, Bhargava P, Bancaud A, Gadal O (2013) “Systematic characterization of the conformation and dynamics of budding yeast chromosome XII” Journal of Cell Biology DOI: 10.1083/jcb.201208186. 
2- Hajjoul H, Mathon J, Ranchon H, Goiffon I, Mozziconacci J, Albert B, Carrivain P Victor JM, Gadal O, Bystrikcy K, Bancaud A (2013) "High throughput chromatin motion tracking in living yeast reveals the flexibility of the fiber throughout the genome" accepted in Genome Research

Contact : Aurélien Bancaud, abancaud@laas.fr