Biological & Soft Matter Seminar: Moving together to stay in place: Stochastic analysis of nuclear chromatin dynamics

Abstract:

Major research advances have been achieved in linking the spatial organization of chromatin to various genetic functions and epigenetic states. However, spatial organization is both created and destroyed through motion – random diffusion will cause the loss of spatial order, while controlled dynamics enable the changing of conformational states and relaxation of structural stresses. Chromosomes, as microscopic entities, are in a continuously diffusing environment, and in fact also continuously move themselves. This challenges the stability of chromosomal spatial order in the interphase nucleus, and as a result the maintenance of epigenetic traits that are dependent on this organization. However, we are currently lacking a comprehensive description of chromatin dynamics throughout the cellular life cycle and on different spatial scales.

To shed light on the how and whether chromosomal organization maintenance is balanced with continuous motion we measured and analyzed the motion of different genomic regions in time. Genomic loci were fluorescently labeled and tracked with live cell fluorescent microscopy, and their trajectories in time were extracted. Once these trajectories were gathered, it was possible to dive into the stochastic data and identify the various dynamic characteristics of chromatin motion.

Mathematical analysis shows that the diffusion of loci is described by fractional Brownian motion, compatible with polymer models. We find constraining short range correlations between loci pairs, while long range anisotropic correlations lead to the identification of a novel super imposed diffusive process. Surprisingly, down regulation of Lamin A, a central structural protein, transforms dynamics into rapid normal diffusion, in contradiction to naïve physical expectation. The emerging dynamical picture of chromatin has significant biological implications regarding both the maintenance and modification of nuclear organization. 

Seminar Organizer: Guy Yaacoby