ArticleNature structural & molecular biology2010
Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia.
Article in Nature structural & molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 172 citations in OpenAlex.
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.Molecular cell · 2026Article
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.bioRxiv : the preprint server for biology · 2026Article
- Chromatin binding and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation.Genes & development · 2026Article
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- A novel human acute myeloid leukemia cell line SDEY-AML1 with KMT2A: MLLT3, IKZF1: EVX1 fusions exhibits high tumorigenicity in NSG mice.Scientific reports · 2026Article
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Article
- KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.Molecular oncology · 2025Article
- Deficiency of TET2-mediated KMT2D self-transcription confers a targetable vulnerability in hepatocellular carcinoma.PNAS nexus · 2024Article
- HBO1, a MYSTerious KAT and its links to cancer.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.Nature communications · 2023Article
- Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers.Cellular and molecular life sciences : CMLS · 2023Article
- Role of the MOZ/MLL-mediated transcriptional activation system for self-renewal in normal hematopoiesis and leukemogenesis.The FEBS journal · 2022Review
- Pathogenic Mechanisms in Acute Myeloid Leukemia.Current treatment options in oncology · 2022Review
- Bioinformatic Analyses of Broad H3K79me2 Domains in Different Leukemia Cell Line Data Sets.Cells · 2022Article
- Small-Molecule Inhibitors of the MLL1 CXXC Domain, an Epigenetic Reader of DNA Methylation.ACS medicinal chemistry letters · 2022Article
- Missense variants causing Wiedemann-Steiner syndrome preferentially occur in the KMT2A-CXXC domain and are accurately classified using AlphaFold2.PLoS genetics · 2022Article
- Direct targeted therapy for MLL-fusion-driven high-risk acute leukaemias.Clinical and translational medicine · 2022Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The gene MLL (encoding the protein mixed-lineage leukemia) is the target of chromosomal translocations that cause leukemias with poor prognosis. All leukemogenic MLL fusion proteins retain the CXXC domain, which binds to nonmethylated CpG DNA sites. We present the solution structure of the MLL CXXC domain in complex with DNA, showing how the CXXC domain distinguishes nonmethylated from methylated CpG DNA. On the basis of the structure, we generated point mutations that disrupt DNA binding. Introduction of these mutations into the MLL-AF9 fusion protein resulted in increased DNA methylation of specific CpG nucleotides in Hoxa9, increased H3K9 methylation, decreased expression of Hoxa9-locus transcripts, loss of immortalization potential, and inability to induce leukemia in mice. These results establish that DNA binding by the CXXC domain and protection against DNA methylation is essential for MLL fusion leukemia. They also provide support for viewing this interaction as a potential target for therapeutic intervention.
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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.