The DNA in a human cell which is ~2 meters long is packed in a ~10 μm nucleus. It is immersed in a condensed soup of proteins, RNA and enzymes and it is highly dynamic. Nevertheless, it must stay organized to prevent chromosome entanglement and for ensuring proper genome expression.
Studying the DNA (or chromatin) organization requires to use high spatial and temporal resolutions combined with live-cell imaging. We combine comprehensive live-cell and molecular methods in order to explore the structure. As part of the study, we use single particle tracking and perform diffusion analysis. Interesting sub-diffusion is identified with bi-modal behavior that we fit to a model that takes into account the existence of significant forces in the nucleus that acts on chromatin.
The results allowed us to identify the protein lamin A as the main player that affect the chromatin organization in the nucleus. It forms chromatin loops in the whole nuclear volume thereby restricting the chromatin dynamics and increasing its elasticity and rigidity. Together with other mechanisms, it also takes part in controlling gene expression.
It emphasizes the importance of the multi-scale organization of the genome in the nucleus.