ArticleNature cell biology2023
Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 36 citations in OpenAlex.
- Current and future therapies for acute myeloblastic leukemia.Journal of hematology & oncology · 2026Review
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Histone Methylation and Chromatin Remodeling in Non-Small Cell Lung Cancer: Mechanisms of Oncogenesis and Emerging Therapeutic Strategies.Biomedicines · 2026Review
- Article
- Optimal donor selection for transplant to reduce GVHD risk and augment graft-versus-malignancy efficacy.Current opinion in immunology · 2026Review
- A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma.Oncogene · 2026Article
- Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.The FEBS journal · 2026Review
- PRC2 loss impairs small cell lung cancer tumorigenesis and enhances sensitivity to G9a/GLP inhibition.Communications biology · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives.Oncology research · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Catalytic Inhibition of KAT6/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia.Cancer discovery · 2025Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- IFITM3 enhances immunosensitivity via MHC-I regulation and is associated with the efficacy of anti-PD-1/-L1 therapy in SCLC.Molecular cancer · 2025Article
- Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.Haematologica · 2025Article
- Targeted disruption of PRC1.1 complex enhances bone remodeling.Nature communications · 2025Article
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
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20 authors at 7 institutions in 2 countries.
Funding
Abstract
Precise control of activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent promoters is essential for normal development and frequently corrupted in cancer. By coupling a cell surface readout of bivalent MHC class I gene expression with whole-genome CRISPR-Cas9 screens, we identify specific roles for MTF2-PRC2.1, PCGF1-PRC1.1 and Menin-KMT2A/B complexes in maintaining bivalency. Genetic loss or pharmacological inhibition of Menin unexpectedly phenocopies the effects of polycomb disruption, resulting in derepression of bivalent genes in both cancer cells and pluripotent stem cells. While Menin and KMT2A/B contribute to H3K4me3 at active genes, a separate Menin-independent function of KMT2A/B maintains H3K4me3 and opposes polycomb-mediated repression at bivalent genes. Release of KMT2A from active genes following Menin targeting alters the balance of polycomb and KMT2A at bivalent genes, facilitating gene activation. This functional partitioning of Menin-KMT2A/B complex components reveals therapeutic opportunities that can be leveraged through inhibition of Menin.
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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.