Study of Nuclear Organization through the Dynamic Properties of Chromatin

Chromosomes occupy specific nuclear volumes called chromosome territories and their motion is highly constrained. Little is known about which proteins and structures organize chromosome territories. A major object of our research is to understand the biophysical mechanisms that maintain this organization. We turned to study the diffusion properties of genome in order to shed light on this maintenance mechanism. The diffusion character of species depends on its properties and on the environment, thereby providing an excellent method for studying the nuclear maintenance mechanism. We examined genome mobility by focusing on three different genomic elements: telomeres, centromeres and specific gene loci. We developed method that allows measuring the diffusion in time-range of 10−2 - 104 sec. Such broad time range allowed us to identify the transient anomalous diffusion of different genomic regions that could not be identified by other techniques. Anomalous diffusion usually depends on environmental constrains, such as temporal binding. Therefore, we propose a model for chromatin organization maintenance in the nucleus that is based on temporal binding of chromatin to itself, or to other nuclear entities. In order to prove this hypothesis, we decided to focus on identifying the possible molecular source of the suggested binding. We conduct our research on measuring the effect of loss of Lamin A on chromatin's diffusion properties. We found that telomeres and centromes motion in cells without Lamin A is ∼8 times less constrained compared to normal cells. It also shows normal diffusion, while in normal cells diffusion was found anomalous. Based on our results we can conclude that lack of Lamin A leads to looser chromatin. Finding other proteins that are responsible for such binding is a great challenge that we are now pursuing.