ArticleProceedings of the National Academy of Sciences of the United States of America2022
Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 107 citations in OpenAlex.
- Stepwise reorganization of chromosome conformation and nuclear organization during stem cell differentiation.bioRxiv : the preprint server for biology · 2026Article
- Systematic evaluation of the heterogeneity of topologically associating domain boundaries in a large genomic context in humans.NAR genomics and bioinformatics · 2026Article
- Origins and consequences of oncogenic 3D chromatin remodelling.Nature reviews. Cancer · 2026Review
- Epigenetic Landscape of H3K27ac, H3K27me3, H3K4me1, and H3K4me3 Marks in Channel Catfish Following Βeta Glucan Exposure.International journal of molecular sciences · 2026Article
- Polycomb-mediated 3D-genome organization controls replication timing.Science advances · 2026Article
- The Hippo signaling pathway in pediatric brain tumors: molecular mechanisms and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs.Nature genetics · 2026Article
- Polycomb chromatin topology enables long-range enhancer recruitment during craniofacial development.Nature communications · 2026Article
- Polycomb-mediated 3D chromatin interactions in gene regulation.Current opinion in genetics & development · 2026Review
- Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes.Molecular cell · 2026Article
- Unique territorial and compartmental organization of chromosomes in the holocentric silkworm.The EMBO journal · 2026Article
- Trimodal single-cell profiling of transcriptome, epigenome and 3D genome in complex tissues with scHiCAR.Nature biotechnology · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Epigenome and interactome profiling uncovers principles of distal regulation in the barley genome.Cell genomics · 2026Article
- Article
- Bridging MBD3 functions in developmental biology and glioma heterogeneity to immune remodeling with future perspectives.Frontiers in immunology · 2026Review
- Chromatin folding by the Polycomb group proteins and its elusive role in epigenetic repression.The FEBS journal · 2026Review
- Oncogenic activation of EVC/EVC2 defines a therapeutically targetable subset of acute myeloid leukemia.Leukemia · 2026Article
- 3D genome folding in epigenetic regulation and cellular memory.Trends in cell biology · 2026Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cell (ESC) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling progressive spreading of H3K27me3 on the linear genome. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remain unclear. Here, we apply H3K27me3 HiChIP, a protein-directed chromosome conformation method, and optical reconstruction of chromatin architecture to profile long-range Polycomb-associated DNA loops that span tens to hundreds of megabases across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. We find that H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes. Genetic deletion of H3K27me3 loop anchors results in disruption of spatial contact between distant loci and altered H3K27me3 in cis, both locally and megabases away on the same chromosome. In mouse embryos, loop anchor deletion leads to ectopic activation of the partner gene, suggesting that Polycomb-associated loops control gene silencing during development. Further, we find that alterations in PRC2 occupancy resulting from an RNA binding–deficient EZH2 mutant are accompanied by loss of Polycomb-associated DNA looping. Together, these results suggest PRC2 uses RNA binding to enhance long-range chromosome folding and H3K27me3 spreading. Developmental gene loci have unique roles in Polycomb spreading, emerging as important architectural elements of the epigenome.
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Registered trials
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.