Publication Date:
2022-05-26
Description:
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nagashima, R., Hibino, K., Ashwin, S. S., Babokhov, M., Fujishiro, S., Imai, R., Nozaki, T., Tamura, S., Tani, T., Kimura, H., Shribak, M., Kanemaki, M. T., Sasai, M., & Maeshima, K. Single nucleosome imaging reveals loose genome chromatin networks via active RNA polymerase II. Journal of Cell Biology, 218(5), (2019):1511-1530, doi:10.1083/jcb.201811090.
Description:
Although chromatin organization and dynamics play a critical role in gene transcription, how they interplay remains unclear.
To approach this issue, we investigated genome-wide chromatin behavior under various transcriptional conditions in living
human cells using single-nucleosome imaging. While transcription by RNA polymerase II (RNAPII) is generally thought to
need more open and dynamic chromatin, surprisingly, we found that active RNAPII globally constrains chromatin movements.
RNAPII inhibition or its rapid depletion released the chromatin constraints and increased chromatin dynamics. Perturbation
experiments of P-TEFb clusters, which are associated with active RNAPII, had similar results. Furthermore, chromatin
mobility also increased in resting G0 cells and UV-irradiated cells, which are transcriptionally less active. Our results
demonstrated that chromatin is globally stabilized by loose connections through active RNAPII, which is compatible with
models of classical transcription factories or liquid droplet formation of transcription-related factors. Together with our
computational modeling, we propose the existence of loose chromatin domain networks for various intra-/interchromosomal
contacts via active RNAPII clusters/droplets.
Description:
We thank Dr. Y. Hiromi, Dr. S. Hirose, Dr. H. Seino, and Dr. S. Ide for critical reading of this manuscript. We thank Dr. S. Ide, Dr. D. Kaida, Dr. T. Nagai, Dr. V. Doye, Dr. G. Felsenfeld, and Dr. K. Horie for valuable help and materials. We also thank the Maeshima laboratory members for helpful discussions and support.
R. Imai and T. Nozaki are Japan Society for the Promotion of Science Fellows. R. Nagashima was supported by 2017 SOKENDAI Short-Stay Study Abroad Program. This work was supported by a Japan Society for the Promotion of Science grant (16H04746), Takeda Science Foundation, RIKEN Pioneering Project, a Japan Science and Technology Agency Core Research for Evolutional Science and Technology grant (JPMJCR15G2), a National Institute of General Medical Sciences grant (R01-GM101701), and National Institute of Genetics JOINT (2016-A2 (6)).
Repository Name:
Woods Hole Open Access Server
Type:
Article
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