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Anisha Shakya
첨단연성물질 연구단
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Liquid-Liquid Phase Separation of Histone Proteins in Cells: Role in Chromatin Organization

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Title
Liquid-Liquid Phase Separation of Histone Proteins in Cells: Role in Chromatin Organization
Author(s)
Anisha Shakya; Seonyoung Park; Neha Rana; John Thomas King
Publication Date
2020-02
Journal
BIOPHYSICAL JOURNAL, v.118, no.3, pp.753 - 764
Publisher
CELL PRESS
Abstract
© 2019 Biophysical SocietyLiquid-liquid phase separation (LLPS) of proteins and nucleic acids has emerged as an important phenomenon in membraneless intracellular organization. We demonstrate that the linker histone H1 condenses into liquid-like droplets in the nuclei of HeLa cells. The droplets, observed during the interphase of the cell cycle, are colocalized with DNA-dense regions indicative of heterochromatin. In vitro, H1 readily undergoes LLPS with both DNA and nucleosomes of varying lengths but does not phase separate in the absence of DNA. The nucleosome core particle maintains its structural integrity inside the droplets, as demonstrated by FRET. Unexpectedly, H2A also forms droplets in the presence of DNA and nucleosomes in vitro, whereas the other core histones precipitate. The phase diagram of H1 with nucleosomes is invariant to the nucleosome length at physiological salt concentration, indicating that H1 is capable of partitioning large segments of DNA into liquid-like droplets. Of the proteins tested (H1, core histones, and the heterochromatin protein HP1α), this property is unique to H1. In addition, free nucleotides promote droplet formation of H1 nucleosome in a nucleotide-dependent manner, with droplet formation being most favorable with ATP. Although LLPS of HP1α is known to contribute to the organization of heterochromatin, our results indicate that H1 also plays a role. Based on our study, we propose that H1 and DNA act as scaffolds for phase-separated heterochromatin domains
URI
https://pr.ibs.re.kr/handle/8788114/7014
ISSN
0006-3495
Appears in Collections:
Center for Soft and Living Matter(첨단연성물질 연구단) > Journal Papers (저널논문)
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