Kazuhiro Maeshima - Chromatin behavior during cell cycle revealed by single-nucleosome imaging/tacking
Wolfson Lecture Theatre, Yusuf Hamied Department of Chemistry, University of Cambridge
Lensfield Road Cambridge CB2 1EW United KingdomKazuhiro Maeshima
National Institute of Genetics and Sokendai (Graduate University for Advanced Studies), Mishima, Shizuoka, Japan
Dynamic chromatin behavior plays a critical role in various genome functions (1). However, it remains unclear how chromatin behavior changes during cell cycle. In interphase, the nucleus enlarges, and genomic DNA doubles. It was previously reported that chromatin movements varied during interphase when measured using a minute or longer time-scale. However, using single-nucleosome imaging/tracking (2), we unveil that local chromatin motion on a second time-scale remained steady throughout G1, S and G2 phases in live human cells (3). This motion mode appeared to change beyond this time-scale. A defined genomic region also behaved similarly during interphase. Combined with Brownian dynamics modeling, our results suggest that this steady-state chromatin motion was mainly driven by thermal fluctuations. Steady-state motion temporarily increased following a DNA damage response. Our findings support the viscoelastic properties of chromatin. We propose that the observed steady-state chromatin motion allows cells to conduct housekeeping functions, such as transcription and DNA replication, under similar environments during interphase (3).
Furthermore, during mitosis, copied genome chromatin must be faithfully transmitted into two daughter cells as condensed chromosomes, whose morphology looks totally different from interphase ones. Our single-nucleosome imaging/tracking demonstrated that mitotic chromatin is much more constrained than interphase chromatin. Condensins and local nucleosome-nucleosome are major constraining factors during mitosis.
References:
1, Maeshima, K., Iida, S., Tamura, S. (2021) Cold Spring Harbor Perspectives in Biology. a040675.
2, Ide, S., Tamura, S., Maeshima, K. (2022) BioEssays. 44, 2200043.
3, Iida, S. et al. (2022) Science Advances. 8, eabn5626