Centromere and telomere dynamics reveal heterogeneity of the human cell nucleus

The human genome contains genetic information essential for life, controlling all cellular processes via the central dogma of biology. It is a canonical example of a living polymer, yet the physical principles underlying its dynamical self-organization in the cell nucleus remain unknown. In this work, we study motions of centromeres and telomeres - the centers and free ends of chromosomes - at short time scales of seconds in live human cells. Our findings reveal a tenfold difference in their displacements, exceeding by far predictions of polymer theories. Remarkably, we find that this unexpectedly large difference arises due to centromere and telomere localization in unique nuclear environments, distinct in both their biological activity and physical properties. We locate the former in the genome's silenced parts, the latter in its transcriptionally active parts. Moreover, our data show that centromeres are embedded in a solid-like environment, while telomeres’ surroundings are liquid-like, directly affecting the timescales and length scales of their respective motions. Our results suggest a key role of nuclear heterogeneity in genome dynamics, which we corroborate by biochemical perturbations of nuclear structures such as heterochromatin and nuclear speckles. Finally, upon homogenizing the nuclear environment by a hypoosmotic shock, we observe equal centromeric and telomeric motions, confirming our hypothesis. Our observations show that the nuclear environment directly impacts timescales and length scales of local genomic motions, which may affect the spatiotemporal gene regulation across the cell nucleus [Clavijo AS, Ionov S & Zidovska A, Submitted].