ArticleProceedings of the National Academy of Sciences of the United States of America2023
HP1-driven phase separation recapitulates the thermodynamics and kinetics of heterochromatin condensate formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Chromatin remodelling: a driving force in reverse mechanotransduction.RNA biology · 2026Review
- Mechanical regulation of cell memory.Nature structural & molecular biology · 2026Review
- Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3.Nucleic acids research · 2026Article
- Mixing chromatin fibers with different nucleosome repeat lengths changes dynamics of chromatin phase separation.The Journal of biological chemistry · 2026Article
- Modeling the spatial organization of replicated chromosomes in yeast reveals a loose asymmetric cohesion between sister chromatids.Nucleic acids research · 2026Article
- Phase separation of ecDNA condensates establishes in-trans contact domains that boost selective MYC regulatory interactions.Nature communications · 2026Article
- Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the ALT pathway.The EMBO journal · 2026Article
- Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- In vitro reconstitution of heterochromatin compartments reveals the spontaneous formation of tunable liquid-liquid interfaces.Nucleic acids research · 2026Article
- Sequence-dependent co-condensation of Lsr2 with DNA elucidates the mechanism of genome compaction in Mycobacterium tuberculosis.Nucleic acids research · 2026Article
- Phase separation as an emerging regulatory framework in antibody class switching and genome stability.Frontiers in immunology · 2026Review
- Genome-wide modeling of DNA replication in space and time confirms the emergence of replication specific patterns in vivo in eukaryotes.Genome biology · 2025Article
- Decoding the role of DNA sequence on protein-DNA co-condensation.PLoS computational biology · 2025Article
- Hierarchical interactions between nucleolar and heterochromatin condensates are mediated by a dual-affinity protein.Nature cell biology · 2025Article
- Interactions between the genome and the nuclear lamina are multivalent and cooperative.Nature structural & molecular biology · 2025Article
- Protein language model identifies disordered, conserved motifs implicated in phase separation.eLife · 2025Article
- Review
- Biomolecular condensates in plant immunity.Cell host & microbe · 2025Review
- Protein-DNA co-condensation is prewetting to a collapsed polymer.Biophysical journal · 2025Article
- HP1 loses its chromatin clustering and phase separation function across evolution.Nature communications · 2025Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding of Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid-liquid phase separation properties in vitro, its mechanistic impact on the structure and dynamics of PCH condensate formation in vivo remains largely unresolved. Here, using a minimal theoretical framework, we systematically investigate the mutual coupling between self-interacting HP1-like molecules and the chromatin polymer. We reveal that the specific affinity of HP1 for H3K9me2/3 loci facilitates coacervation in nucleo and promotes the formation of stable PCH condensates at HP1 levels far below the concentration required to observe phase separation in purified protein assays in vitro. These heterotypic HP1-chromatin interactions give rise to a strong dependence of the nucleoplasmic HP1 density on HP1-H3K9me2/3 stoichiometry, consistent with the thermodynamics of multicomponent phase separation. The dynamical cross talk between HP1 and the viscoelastic chromatin scaffold also leads to anomalously slow equilibration kinetics, which strongly depend on the genomic distribution of H3K9me2/3 domains and result in the coexistence of multiple long-lived, microphase-separated PCH compartments. The morphology of these complex coacervates is further found to be governed by the dynamic establishment of the underlying H3K9me2/3 landscape, which may drive their increasingly abnormal, aspherical shapes during cell development. These findings compare favorably to 4D microscopy measurements of HP1 condensate formation in live
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.