Speaker
Description
"Replication-dependent histone (Repli-Histo) labeling specifically visualizes physical properties of euchromatin/heterochromatin in living human cells.
Katsuhiko Minami1, 2, Satoru Ide1, 2, Sachiko Tamura1, and Kazuhiro Maeshima1, 2
1 Genome Dynamics Laboratory, National Institute of Genetics
2 Graduate Institute for Advanced Studies, SOKENDAI
Abstract
Recent advanced imaging studies have revealed that euchromatin in higher eukaryotic cells forms condensed liquid-like domains with very limited ""open"" regions [1-3]. While such condensed chromatin organization provides a higher-order regulation of genome functions, it raises intriguing questions: How are euchromatin and heterochromatin physically different in living cells? How relevant is the difference to the regulation of genome functions?
To approach these questions, we have developed two imaging techniques. The first is single-nucleosome imaging and tracking [2, 4], which present the physical nature of chromatin in living cells. Using this, we have demonstrated that nucleosomes in living human cells fluctuate dynamically, mainly driven by thermal fluctuation [5]. The second technique is a novel chromatin labeling method, replication-dependent histone labeling (Repli-Histo labeling), which can specifically label four groups of genome regions from euchromatin (early replicated regions) to heterochromatin (late replicated regions) based on DNA replication-timing. Combining our Repli-Histo labeling with the single-nucleosome imaging, we have found that more euchromatic regions show larger local chromatin motion, whereas more heterochromatic regions have smaller motion. Interestingly, these properties seem to be maintained throughout interphase cell cycle. These findings also reveal that chromatin regions with earlier replication timing have greater chromatin motion. Since local chromatin motion can regulate the chromatin accessibility [6, 7], our study suggest that the genome-wide landscape of local chromatin motion in euchromatin and heterochromatin can regulate DNA replication timing.
[1] Maeshima, K., Iida, S., Shimazoe, M. A., Tamura, S. & Ide, S. Trends in Cell Biology 34, 7-17 (2024)
[2] Nozaki, T. et al. Science Advances 9, eadf1488 (2023)
[3] Miron, E. et al. Science Advances 6, eaba8811 (2020)
[4] Ide, S., Tamura, S. & Maeshima, K. BioEssays 44, 2200043 (2022)
[5] Iida, S. et al. Science advances 8, eabn5626 (2022)
[6] Hihara, S. et al. Cell Reports 2, 1645–1656 (2012)
[7] Maeshima, K. et al. Journal of Physics: Condensed Matter 27, 064116 (2015)
"
