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Quadruplex Folding of DNA Promotes the Condensation of Linker Histones via Liquid-Liquid Phase Separation

preprint
revised on 12.02.2020, 05:35 and posted on 12.02.2020, 08:54 by Masahiro Mimura, Shunsuke Tomita, Yoichi Shinkai, Kentaro Shiraki, Ryoji Kurita

Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. Fluidity measurements inside the droplets and binding assays using G-quadruplex-selective probes demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. The dissolution of the droplets in the presence of additives indicated that in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation. Given that DNA quadruplex structures are well documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.

Funding

JSPS KAKENHI (18H02383, 19K22377)

a DAICENTER project grant from the DBT

History

Email Address of Submitting Author

s.tomita@aist.go.jp

Institution

Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology

Country

Japan

ORCID For Submitting Author

0000-0002-0586-6976

Declaration of Conflict of Interest

The authors declare no competing financial interest.

Version Notes

First version

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