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Heterogeneous fluid-like movements of chromatin and their implications to transcription

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Abstract

Eukaryotic chromatin is a complex of genome DNA and associated proteins, and its structure and dynamics play a crucial role in regulating DNA functions. Chromatin takes rather irregular structures in the nucleus and exhibits heterogeneous sub-diffusive movements as polymers fluctuating in a fluid state. Using genome-wide single-nucleosome tracking data, heterogeneity of movements was statistically analyzed, which categorized chromatin into two types: slow chromatin that moves under structurally constrained environments and fast chromatin that moves with less constraints. Interactions of chromatin to various protein factors determine the motional constraints. For example, loss of the cohesin complex that bundles the chromatin chains reduces the motional constraints and increases the population of fast chromatin. Another example is the transcriptional machinery. While it was previously thought that the transcriptional activity is associated with more open and dynamic chromatin structure, recent studies suggested a more nuanced role of transcription in chromatin dynamics: dynamic association/dissociation of active RNA polymerase II (RNAPII) and other transcription factors and Mediators (TF-Meds) transiently bridges transcriptionally active DNA regions, which forms a loose network of chromatin and constrains chromatin movement, enhancing the slow chromatin population. This new view on the dynamical effects of transcription urges a reflection on the traditional model of transcription factories and invites the more recent models of condensates/phase-separated liquid droplets of RNAPII, transcription factors, and Mediators. The combined procedure of genome-wide single-nucleosome tracking and its statistical analysis would unveil heterogeneity in the chromatin movement, which should provide a key to understanding the relations among chromatin dynamics, structure, and function.

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Acknowledgments

We are grateful to all the collaborators Nozaki et al. (2017), Nagashima et al. (2019), and Ashwin et al. (2019) for their contribution, and Sasai and Maeshima Lab members for helpful discussion.

Funding

This work was supported by JST-CREST Grant JPMJCR15G2; the Riken Pioneering Project; JSPS-KAKENHI Grants JP19H01860, 19H05258, JP16H04746, 16H06279 (PAGS), and 19H05273; the Takeda Science Foundation; and NIG-JOINT 2016-A2 (6).

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  1. Department of Applied Physics, Nagoya University, Nagoya, 464-8603, Japan

    S. S. Ashwin & Masaki Sasai

  2. National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan

    Kazuhiro Maeshima

  3. Department of Genetics, SOKENDAI, Mishima, Shizuoka, 411-8540, Japan

    Kazuhiro Maeshima

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  1. S. S. Ashwin
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Ashwin, S.S., Maeshima, K. & Sasai, M. Heterogeneous fluid-like movements of chromatin and their implications to transcription. Biophys Rev 12, 461–468 (2020). https://doi.org/10.1007/s12551-020-00675-8

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