The genome in the nucleus: snaky, dynamic and yet organized
The DNA in a human cell is ~3 meters long. It is dynamic and although there are no definite structures that maintain the order in the nucleus, the genome is well organized. What are the mechanisms that organizes the DNA in the nucleus?
Dynamic methods in live cells are ideal for studying the genome organization, as it is mainly made of soft-matter that have no definite structure.
We used single particle tracking (SPT) and continuous photobleacing (CP) that are adequate for live-cell imaging and the data is analyzed according to diffusion analysis methods. In normal cells, all the sites in the genome exhibit anomalous diffusion (viscoelastic) with a power law of ~0.3-0.5 and the diffusion was found to belong to the family of fractional Brownian motion anomalous diffusion.
We rationalized that the source of the viscoelasticity is a protein that can temporarily bind chromatin. We identified one source protein (lamin A) that dramatically affects the diffusion pattern and leads to a phase transition from viscoelastic to viscous diffusion when its expression is inhibited. We suggest a rather simple mechanism that explains the organization maintenance of the chromosomal territories. It is based on the properties of the DNA itself organized by cross-links of lamin A and mediated by other proteins.