Organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Phase-separation has been implicated in heterochromatin formation, but it is unclear how phase-separated condensates can contribute to stable repression, particularly for heritable epigenetic changes. Polycomb complex PRC1 is key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we show that PRC1 forms multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. We show that inducing Polycomb phase-separation can cause chromatin compaction, but polycomb condensates are dispensable for maintenance of the compacted state. Our data and simulations are consistent with a model in which the time integral of Polycomb phase-separation is progressively recorded in repressive histone marks, which subsequently drive compaction. These findings link the equilibrium thermodynamics of phase-separation with the fundamentally non-equilibrium concept of epigenetic memory.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497513 | PMC |
| http://dx.doi.org/10.1038/s41467-021-26147-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Double-strand breaks in facultative heterochromatin require specific movements and chromatin changes for efficient repair.
Nat Commun
October 2024
Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands.
Article Synopsis
- DNA double-strand breaks (DSBs) are critical to repair for maintaining genome stability, with different chromatin types potentially requiring distinct repair mechanisms.
- In a study involving Drosophila melanogaster, it was found that DSBs in facultative heterochromatin quickly move outside of specialized structures called polycomb bodies and this movement corresponds with a decrease in a specific histone mark, H3K27me3.
- The research indicates that the histone demethylase dUtx is essential for this process, as its absence disrupts both the movement of DSBs and the completion of repair via homologous recombination in heterochromatic regions.
Calcium modulates the tethering of BCOR-PRC1.1 enzymatic core to KDM2B via liquid-liquid phase separation.
Commun Biol
September 2024
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Article Synopsis
- BCOR-PRC1.1 recruitment to non-methylated CpG islands via KDM2B is crucial for controlling transcription during development and cancer, but the regulatory mechanisms are still not fully understood.
- Research highlights the significance of negatively charged Poly-D/E regions in BCOR for binding to KDM2B and how these regions inhibit liquid-liquid phase separation (LLPS) for BCOR/PCGF1.
- The study suggests that neutralizing the negative charges with calcium (Ca) alters the interaction between BCOR/PCGF1 and KDM2B, promoting the formation of liquid-like droplets and enhancing the recruitment of the BCOR-PRC1.1 core to KDM2B target sites.
PICKLE-mediated nucleosome condensing drives H3K27me3 spreading for the inheritance of Polycomb memory during differentiation.
Mol Cell
September 2024
State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address:
Article Synopsis
- H3K27me3 is essential for maintaining chromatin silencing in both animals and plants, but the process of how the Polycomb repressive complex 2 (PRC2) spreads this modification to unmodified nucleosomes is not well understood.
- Research in Arabidopsis thaliana shows that the chromatin remodeler PICKLE (PKL) is key for H3K27me3 spreading, helping to maintain cell identity during differentiation by associating with PRC2 in spreading regions.
- By increasing nucleosome density through its ATPase function, PKL allows PRC2 to access unmodified nucleosomes, which is crucial for the effective spreading of H3K27me3 and the establishment of re
Variant PRC1 subunit RYBP/YAF2 forms condensate with RING1B and promotes H2AK119ub deposition.
Sci China Life Sci
September 2024
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.
Nucleic Acids Res
June 2024
Department of Biological Sciences & Institute of Molecular Biology and Genetics (IMBG), Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08826, Korea.
Article Synopsis
- BRCA2 plays a vital role in maintaining proper telomere function, and its absence causes telomeric damage, leading cells to use alternative mechanisms like break-induced replication (BIR) to manage telomeres.
- The stabilization of telomeric G-quadruplexes (G4) when BRCA2 is depleted results in the accumulation of TERRA-R-loops, which trigger liquid-liquid phase separation (LLPS) and formation of specific bodies (APBs) associated with ALT.
- Research suggests that targeting the interactions of telomeric G4 and TERRA-R-loops could be a promising strategy for treating cancers, particularly those with BRCA2 mutations that display ALT characteristics.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!