ArticleProceedings of the National Academy of Sciences of the United States of America2016
Propagation of trimethylated H3K27 regulated by polycomb protein EED is required for embryogenesis, hematopoietic maintenance, and tumor suppression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 27 citations in OpenAlex.
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- Article
- Functional analysis of human EED variants using Drosophila.Genetics · 2025Article
- Article
- Caf1 regulates the histone methyltransferase activity of Ash1 by sensing unmodified histone H3.Epigenetics & chromatin · 2023Article
- Epigenetic regulation of embryonic ectoderm development in stem cell differentiation and transformation during ontogenesis.Cell proliferation · 2023Review
- Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.International journal of molecular sciences · 2022Review
- Loss of microglial EED impairs synapse density, learning, and memory.Molecular psychiatry · 2022Article
- Mechanisms of Polycomb group protein function in cancer.Cell research · 2022Review
- Expression and Function of Nicotinic Acetylcholine Receptors in Induced Regulatory T Cells.International journal of molecular sciences · 2022Article
- KDM4B promotes acute myeloid leukemia associated with AML1-ETO by regulating chromatin accessibility.FASEB bioAdvances · 2021Article
- The language of chromatin modification in human cancers.Nature reviews. Cancer · 2021Review
- Polycomb Gene Silencing Mechanisms: PRC2 Chromatin Targeting, H3K27me3 'Readout', and Phase Separation-Based Compaction.Trends in genetics : TIG · 2021Review
- PRC2 is high maintenance.Genes & development · 2019Review
- Discovery of selective activators of PRC2 mutant EED-I363M.Scientific reports · 2019Article
- Polycomb complexes in normal and malignant hematopoiesis.The Journal of cell biology · 2019Review
- Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation.The Journal of experimental medicine · 2018Article
- Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia.Journal of cancer research and clinical oncology · 2018Article
- Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics.Vaccines · 2017Article
- Acquired expression ofBlood · 2017Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycomb repressive complex 2 (PRC2) catalyzes the monomethylation, dimethylation, and trimethylation of histone H3 Lys27 (H3K27) and acts as a central epigenetic regulator that marks the repressive chromatin domain. Embryonic ectoderm development (EED), an essential component of PRC2, interacts with trimethylated H3K27 (H3K27me3) through the aromatic cage structure composed of its three aromatic amino acids, Phe97, Trp364, and Tyr365. This interaction allosterically activates the histone methyltransferase activity of PRC2 and thereby propagates repressive histone marks. In this study, we report the analysis of knock-in mice harboring the myeloid disorder-associated EED Ile363Met (I363M) mutation, analogous to the EED aromatic cage mutants. The I363M homozygotes displayed a remarkable and preferential reduction of H3K27me3 and died at midgestation. The heterozygotes increased the clonogenic capacity and bone marrow repopulating activity of hematopoietic stem/progenitor cells (HSPCs) and were susceptible to leukemia. Lgals3, a PRC2 target gene encoding a multifunctional galactose-binding lectin, was derepressed in I363M heterozygotes, which enhanced the stemness of HSPCs. Thus, our work provides in vivo evidence that the structural integrity of EED to H3K27me3 propagation is critical, especially for embryonic development and hematopoietic homeostasis, and that its perturbation increases the predisposition to hematologic malignancies.
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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.