Phase-separated chromatin compartments: Orchestrating gene expression through condensation

Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptio...

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Main Authors: Xin Li, Chengzhi Liu, Zhichao Lei, Huan Chen, Liang Wang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Cell Insight
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772892724000683
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author Xin Li
Chengzhi Liu
Zhichao Lei
Huan Chen
Liang Wang
author_facet Xin Li
Chengzhi Liu
Zhichao Lei
Huan Chen
Liang Wang
author_sort Xin Li
collection DOAJ
description Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptional repressors or activators. Phase separation, a well-established biophysical phenomenon, is a key driver of chromatin condensate formation by CAPs. Notably, multivalent CAPs with the ability to engage in diverse interactions promote chromatin compaction, leading to the formation of transcriptionally repressed compartments. Conversely, interactions between intrinsically disordered region (IDR)-containing transcriptional regulators, mediated by their multivalent IDRs, lead to the formation of protein-rich, transcriptionally active droplets on decondensed genomic regions. Interestingly, both repressive heterochromatin and activating euchromatin condensates exhibit spontaneous phase separation and selectively enrich components with concordant transcriptional functions. This review delves into the mechanisms by which transcriptionally repressive CAPs orchestrate the formation of repressed chromatin domains. We further explore how a diverse array of transcription-related CAPs or core histone variants, via phase separation, influence gene expression by inducing erroneous transcription events, regulating expression levels, and facilitating the interconversion of transcriptionally repressed and active regions.
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spelling doaj-art-09dfc96a1e7d4b518a17d482afcfd44b2025-08-20T02:13:23ZengElsevierCell Insight2772-89272024-12-013610021310.1016/j.cellin.2024.100213Phase-separated chromatin compartments: Orchestrating gene expression through condensationXin Li0Chengzhi Liu1Zhichao Lei2Huan Chen3Liang Wang4Beijing Life Science Academy, Beijing, 102209, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, ChinaKey Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, Hubei, ChinaBeijing Life Science Academy, Beijing, 102209, China; Corresponding author.Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China; Corresponding author.Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptional repressors or activators. Phase separation, a well-established biophysical phenomenon, is a key driver of chromatin condensate formation by CAPs. Notably, multivalent CAPs with the ability to engage in diverse interactions promote chromatin compaction, leading to the formation of transcriptionally repressed compartments. Conversely, interactions between intrinsically disordered region (IDR)-containing transcriptional regulators, mediated by their multivalent IDRs, lead to the formation of protein-rich, transcriptionally active droplets on decondensed genomic regions. Interestingly, both repressive heterochromatin and activating euchromatin condensates exhibit spontaneous phase separation and selectively enrich components with concordant transcriptional functions. This review delves into the mechanisms by which transcriptionally repressive CAPs orchestrate the formation of repressed chromatin domains. We further explore how a diverse array of transcription-related CAPs or core histone variants, via phase separation, influence gene expression by inducing erroneous transcription events, regulating expression levels, and facilitating the interconversion of transcriptionally repressed and active regions.http://www.sciencedirect.com/science/article/pii/S2772892724000683Chromatin compartmentalizationPhase separationChromatin-associated proteins/complexesGene expression regulation
spellingShingle Xin Li
Chengzhi Liu
Zhichao Lei
Huan Chen
Liang Wang
Phase-separated chromatin compartments: Orchestrating gene expression through condensation
Cell Insight
Chromatin compartmentalization
Phase separation
Chromatin-associated proteins/complexes
Gene expression regulation
title Phase-separated chromatin compartments: Orchestrating gene expression through condensation
title_full Phase-separated chromatin compartments: Orchestrating gene expression through condensation
title_fullStr Phase-separated chromatin compartments: Orchestrating gene expression through condensation
title_full_unstemmed Phase-separated chromatin compartments: Orchestrating gene expression through condensation
title_short Phase-separated chromatin compartments: Orchestrating gene expression through condensation
title_sort phase separated chromatin compartments orchestrating gene expression through condensation
topic Chromatin compartmentalization
Phase separation
Chromatin-associated proteins/complexes
Gene expression regulation
url http://www.sciencedirect.com/science/article/pii/S2772892724000683
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AT chengzhiliu phaseseparatedchromatincompartmentsorchestratinggeneexpressionthroughcondensation
AT zhichaolei phaseseparatedchromatincompartmentsorchestratinggeneexpressionthroughcondensation
AT huanchen phaseseparatedchromatincompartmentsorchestratinggeneexpressionthroughcondensation
AT liangwang phaseseparatedchromatincompartmentsorchestratinggeneexpressionthroughcondensation