Molecular Mechanism for Genome Organization in the Eukaryotic Nucleus

Abstract

Chromatin and chromosomes in the cell nucleus are organized in a highly ordered yet dynamic structure. Attempts to explain this organization include polymer models and structural models of chromatin anchorage to stable structures, but the principles governing the organization remain unclear. By studying the dynamics of genomic regions in the nucleus of live cells, we show the pivotal role of lamin A in maintaining chromosome organization. Using continuous photobleaching (CP) we show that a significant fraction of cellular lamin A is immobile throughout the whole nucleus. By analyzing the diffusion of telomeres and centromeres we show that lamin A depletion induces a dramatic transition of genome dynamics from slow anomalous diffusion to fast and normal diffusion. These results imply that chromatin organization is actively controlled by inter-chain interactions with lamin A complexes throughout the nucleus. Our results provide a molecular mechanism that can explain the organization of the genome coherently with polymer-based models [1-4] and demonstrate the importance of dynamic measurements in the nucleus for deciphering the genomic organization mechanisms. [1] I. Bronshtein, E. Kepten, I. Kanter, S. Berezin, M. Lindner, Abena B. Redwood, S. Mai, S. Gonzalo, R. Foisner, Y. Shav-Tal and Y. Garini, Nature Communications in press (2015). [2] E. Kepten, A. Weron, I. Bronshtein, K. Burnecki and Y. Garini, Biophysical Journal 109 in press (2015). [3] E. Barkai, Y. Garini, R. Metzler, Physics Today 65, 29-35 (2012). [4] I. Bronstein, Y. Israel, E. Kepten, S. Mai, Y. Shav-Tal, E. Barkai and Y. Garini, Physical Review Letters 103, 018102, (2009).