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Biomolecular liquid‒liquid phase separation associated with repetitive genomic elements

Abstract

Liquid‒liquid phase separation (LLPS) is a fundamental physical phenomenon in which a homogenous liquid spontaneously demixes into distinct liquid phases. A mounting body of evidence has shown that biomolecular LLPS is an essential biological event. In particular, highly condensed environments such as the nucleus are inevitably influenced by biomolecular LLPS, in which extremely long biopolymers, including genomic DNA and associated proteins/RNAs, are present. Given that almost half of the human genome is composed of repetitive elements and that various proteins interact with these sequences in diverse biological contexts, these regions clearly play substantial roles in regulating biomolecular LLPS. In this review, we summarize examples of biomolecular LLPS occurring in repetitive genomic elements. We also discuss how these intrinsic biophysical properties reflect cellular phenotypes by describing intermediate pathways and biomolecular complexes.

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Acknowledgements

This work was supported by JSPS KAKENHI (Grant Numbers 23K13857 to S.A.; 24H02060, 22H02547 to Y.W.I.), RIKEN internal grants (Incentive Research Projects to S.A.), and JST FOREST (Grant Number JPMJFR224L to Y.W.I.).

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Asamitsu, S., Iwasaki, Y.W. Biomolecular liquid‒liquid phase separation associated with repetitive genomic elements. Polym J 57, 785–797 (2025). https://doi.org/10.1038/s41428-025-01036-6

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