ArticleProceedings of the National Academy of Sciences of the United States of America2008
MLL protects CpG clusters from methylation within the Hoxa9 gene, maintaining transcript expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 98 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
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- A characteristic gene expression profile regulated by ACIN1::NUTM1 fusion in a newly identified infant leukaemic cell line and an ACIN1::NUTM1-inducible model.British journal of haematology · 2025Article
- BAHCC1 binds H4K20me1 to facilitate the MCM complex loading and DNA replication.Nature communications · 2025Article
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.Cancer cell international · 2022Review
- Small-Molecule Inhibitors of the MLL1 CXXC Domain, an Epigenetic Reader of DNA Methylation.ACS medicinal chemistry letters · 2022Article
- Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis.Haematologica · 2022Article
- ST8SIA6-AS1 Promotes the Epithelial-to-Mesenchymal Transition and Angiogenesis of Pituitary Adenoma.Journal of oncology · 2022Article
- Dynamics and inhibition of MLL1 CXXC domain on DNA revealed by single-molecule quantification.Biophysical journal · 2021Article
- Genome-wide association studies demonstrate that TASP1 contributes to increased muscle fiber diameter.Heredity · 2021Article
- Insights on the regulation of the MLL/SET1 family histone methyltransferases.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- The Influence of Methylating Mutations on Acute Myeloid Leukemia: Preliminary Analysis on 56 Patients.Diagnostics (Basel, Switzerland) · 2020Article
- Non-coding RNAs in cancers with chromosomal rearrangements: the signatures, causes, functions and implications.Journal of molecular cell biology · 2019Review
- Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators.Current genomics · 2019Review
- Rationale for targeting BCL6 inGenes & development · 2019Article
- miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.The Journal of experimental medicine · 2018Article
- Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin.Cells · 2018Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Homeobox (HOX) genes play a definitive role in determination of cell fate during embryogenesis and hematopoiesis. MLL-related leukemia is coincident with increased expression of a subset of HOX genes, including HOXA9. MLL functions to maintain, rather than initiate, expression of its target genes. However, the mechanism of MLL maintenance of target gene expression is not understood. Here, we demonstrate that Mll binds to specific clusters of CpG residues within the Hoxa9 locus and regulates expression of multiple transcripts. The presence of Mll at these clusters provides protection from DNA methylation. shRNA knock-down of Mll reverses the methylation protection status at the previously protected CpG clusters; methylation at these CpG residues is similar to that observed in Mll null cells. Furthermore, reconstituting MLL expression in Mll null cells can reverse DNA methylation of the same CpG residues, demonstrating a dominant effect of MLL in protecting this specific region from DNA methylation. Intriguingly, an oncogenic MLL-AF4 fusion can also reverse DNA methylation, but only for a subset of these CpGs. This method of transcriptional regulation suggests a mechanism that explains the role of Mll in transcriptional maintenance, but it may extend to other CpG DNA binding proteins. Protection from methylation may be an important mechanism of epigenetic inheritance by regulating the function of both de novo and maintenance DNA methyltransferases.
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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.