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Nanoscale nucleosome dynamics assessed with time-lapse AFM

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Abstract

A fundamental challenge associated with chromosomal gene regulation is accessibility of DNA within nucleosomes. Recent studies performed by various techniques, including single-molecule approaches, led to the realization that nucleosomes are dynamic structures rather than static systems, as was once believed. Direct data are required in order to understand the dynamics of nucleosomes more clearly and to answer fundamental questions, including: What is the range of nucleosome dynamics? Does a non-ATP-dependent unwrapping process of nucleosomes exist? What are the factors facilitating the large-scale opening and unwrapping of nucleosomes? This review summarizes the results of nucleosome dynamics obtained with time-lapse AFM, including a high-speed version (HS-AFM) capable of visualizing molecular dynamics on the millisecond time scale. With HS-AFM, the dynamics of nucleosomes at a sub-second time scale was observed, allowing one to visualize various pathways of nucleosome dynamics, such as sliding and unwrapping, including complete dissociation. Overall, these findings reveal new insights into the dynamics of nucleosomes and the novel mechanisms controlling spontaneous chromatin dynamics.

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Acknowledgments

The work was supported by grants from the National Institutes of Health (5P01GM091743-02 and 5 R01 GM096039-02), the U.S. Department of Energy Grant DE-FG02-08ER64579, the National Science Foundation (EPS—1004094) and the Nebraska Research Initiative. The author thanks Luda Shlyakhtenko for helpful discussions and current and former members of the laboratory for their hard work on the nucleosome project and Rebecca Bigelow for editing of the manuscript.

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  1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, 68198-6025, USA

    Yuri L. Lyubchenko

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Lyubchenko, Y.L. Nanoscale nucleosome dynamics assessed with time-lapse AFM. Biophys Rev 6, 181–190 (2014). https://doi.org/10.1007/s12551-013-0121-3

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