Phase Separation of Chromatin Structure-related Biomolecules: A Driving Force for Epigenetic Regulations

Overview

Journal Curr Protein Pept Sci

Publisher Bentham Science Publishers

Specialty Biochemistry

Date 2024 Mar 29

PMID 38551058

Authors

Jiao Wang

Yuchen Chen

Zixuan Xiao

Xikai Liu

Chengyu Liu

Kun Huang

Hong Chen

Affiliations

Soon will be listed here.

Abstract

Intracellularly, membrane-less organelles are formed by spontaneous fusion and fission of macro-molecules in a process called phase separation, which plays an essential role in cellular activities. In certain disease states, such as cancers and neurodegenerative diseases, aberrant phase separations take place and participate in disease progression. Chromatin structure-related proteins, based on their characteristics and upon external stimuli, phase separate to exert functions like genome assembly, transcription regulation, and signal transduction. Moreover, many chromatin structure-related proteins, such as histones, histone-modifying enzymes, DNA-modifying enzymes, and DNA methylation binding proteins, are involved in epigenetic regulations through phase separation. This review introduces phase separation and how phase separation affects epigenetics with a focus on chromatin structure-related molecules.

References

Pantoja C, Zweckstetter M, Rezaei-Ghaleh N . Dynamical component exchange in a model phase separating system: an NMR-based approach. Phys Chem Chem Phys. 2022; 24(10):6169-6175. DOI: 10.1039/d2cp00042c. View

Mudogo C, Falke S, Brognaro H, Duszenko M, Betzel C . Protein phase separation and determinants of in cell crystallization. Traffic. 2019; 21(2):220-230. DOI: 10.1111/tra.12711. View

Bloom K, Kolbin D . Mechanisms of DNA Mobilization and Sequestration. Genes (Basel). 2022; 13(2). PMC: 8872102. DOI: 10.3390/genes13020352. View

Comert F, Dubin P . Liquid-liquid and liquid-solid phase separation in protein-polyelectrolyte systems. Adv Colloid Interface Sci. 2016; 239:213-217. DOI: 10.1016/j.cis.2016.08.005. View

Rippe K . Liquid-Liquid Phase Separation in Chromatin. Cold Spring Harb Perspect Biol. 2021; 14(2). PMC: 8805649. DOI: 10.1101/cshperspect.a040683. View

Lei Z, Wang L, Kim E, Cho J . Phase separation of chromatin and small RNA pathways in plants. Plant J. 2021; 108(5):1256-1265. DOI: 10.1111/tpj.15517. View

Nsengimana B, Khan F, Awan U, Wang D, Fang N, Wei W . Pseudogenes and Liquid Phase Separation in Epigenetic Expression. Front Oncol. 2022; 12:912282. PMC: 9305658. DOI: 10.3389/fonc.2022.912282. View

Lee D, Strom A, Brangwynne C . The mechanobiology of nuclear phase separation. APL Bioeng. 2022; 6(2):021503. PMC: 9054271. DOI: 10.1063/5.0083286. View

Li X, An Z, Zhang W, Li F . Phase Separation: Direct and Indirect Driving Force for High-Order Chromatin Organization. Genes (Basel). 2023; 14(2). PMC: 9956262. DOI: 10.3390/genes14020499. View

10.

Aguzzi A, Altmeyer M . Phase Separation: Linking Cellular Compartmentalization to Disease. Trends Cell Biol. 2016; 26(7):547-558. DOI: 10.1016/j.tcb.2016.03.004. View

11.

Shen C, Li R, Negro R, Cheng J, Vora S, Fu T . Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome. Cell. 2021; 184(23):5759-5774.e20. PMC: 8643277. DOI: 10.1016/j.cell.2021.09.032. View

12.

Alberti S, Hyman A . Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat Rev Mol Cell Biol. 2021; 22(3):196-213. DOI: 10.1038/s41580-020-00326-6. View

13.

Liu Z, Qin Z, Liu Y, Xia X, He L, Chen N . Liquid‒liquid phase separation: roles and implications in future cancer treatment. Int J Biol Sci. 2023; 19(13):4139-4156. PMC: 10496506. DOI: 10.7150/ijbs.81521. View

14.

Bhat P, Honson D, Guttman M . Nuclear compartmentalization as a mechanism of quantitative control of gene expression. Nat Rev Mol Cell Biol. 2021; 22(10):653-670. DOI: 10.1038/s41580-021-00387-1. View

15.

Li J, Gao J, Wang R . Control of Chromatin Organization and Chromosome Behavior during the Cell Cycle through Phase Separation. Int J Mol Sci. 2021; 22(22). PMC: 8621359. DOI: 10.3390/ijms222212271. View

16.

Pessina F, Gioia U, Brandi O, Farina S, Ceccon M, Francia S . DNA Damage Triggers a New Phase in Neurodegeneration. Trends Genet. 2020; 37(4):337-354. DOI: 10.1016/j.tig.2020.09.006. View

17.

Zhang Y, Kutateladze T . Liquid-liquid phase separation is an intrinsic physicochemical property of chromatin. Nat Struct Mol Biol. 2019; 26(12):1085-1086. PMC: 11514442. DOI: 10.1038/s41594-019-0333-8. View

18.

Ling X, Liu X, Jiang S, Fan L, Ding J . The dynamics of three-dimensional chromatin organization and phase separation in cell fate transitions and diseases. Cell Regen. 2022; 11(1):42. PMC: 9768101. DOI: 10.1186/s13619-022-00145-4. View

19.

Aulas A, Finetti P, Lyons S, Bertucci F, Birnbaum D, Acquaviva C . Revisiting the Concept of Stress in the Prognosis of Solid Tumors: A Role for Stress Granules Proteins?. Cancers (Basel). 2020; 12(9). PMC: 7564653. DOI: 10.3390/cancers12092470. View

20.

Wang B, Zhang L, Dai T, Qin Z, Lu H, Zhang L . Liquid-liquid phase separation in human health and diseases. Signal Transduct Target Ther. 2021; 6(1):290. PMC: 8326283. DOI: 10.1038/s41392-021-00678-1. View