Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

4 - POS

Board 4

TRACKING OF GENOMIC SITES AT NANOSCALE LEADS TO THE UNDERSTANDING OF GENOME ORGANIZATION Irena Bronshtein 1 ; Yuval Garini 1 ; 1 Bar Ilan University, Physics Department and Nanotechnology Institute, Ramat Gan, Center, Israel The organization of the genome in the nucleus is believed to be crucial for cellular functions such as gene regulation and the maintenance of genome integrity along the cell cycle. We used live cell imaging to examine the organization of the genome in living cells. To characterise the dynamic properties of the chromatin, we analysed the diffusion of different genomic sites by measuring their trajectories through Single Particle Tracking (SPT) and thoroughly characterized their diffusion characteristics. Such experimental approach and data analysis enables the characterization of protein interactions with chromatin in live cells in an independent manner to biochemical essays. Chromatin diffusion in differentiated cells was found to be slow and anomalous; in vast contrast, absence of lamin A protein leads to a significant increase in genome mobility and the scanned nuclear volume, and induces a dramatic transition of genome dynamics from slow anomalous diffusion to fast and normal diffusion. Constrained chromatin mobility can have an important part in maintaining the chromosomal territories, which in turn prevents chromosomal entanglement and aberrations. Indeed, we found that lamin A depleted cells have a higher frequency of genomic aberrations compared to normal cells. We propose that chromatin acts like a scaffold folded into loops that are formed by dynamic lamin A crosslinking. This model naturally provides rigidity to the nucleus and explains the mechanism that maintains the chromosomal territories. Altogether, we demonstrate the importance of dynamic measurements in the nucleus for deciphering the mechanisms of genomic organization.


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