ArticleJournal of molecular biology2010
Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 108 citations in OpenAlex.
- Characterizing the impact of MLL fusion variants and fusion partners on leukemia plasticity using a human CRISPR-engineered MLL-rearranged leukemia model.Neoplasia (New York, N.Y.) · 2026Article
- Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.The FEBS journal · 2026Review
- Only InfantInternational journal of molecular sciences · 2024Article
- The KMT2A/MLL consensus gene structure: a comprehensive update for research and diagnostic implications.Leukemia · 2024Article
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- Loss of SMAD1 in acute myeloid leukemia withFrontiers in oncology · 2024Article
- Roles and Regulation of H3K4 Methylation During Mammalian Early Embryogenesis and Embryonic Stem Cell Differentiation.Advances in experimental medicine and biology · 2024Review
- New twists of a TAIL: novel insights into the histone binding properties of a highly conserved PHD finger cluster within the MLR family of H3K4 mono-methyltransferases.Nucleic acids research · 2023Article
- Non-histone binding functions of PHD fingers.Trends in biochemical sciences · 2023Review
- The KMT2A recombinome of acute leukemias in 2023.Leukemia · 2023Article
- RNA binding induces an allosteric switch in Cyp33 to repress MLL1-mediated transcription.Science advances · 2023Article
- Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation.Nucleic acids research · 2022Article
- MLL1 is required for maintenance of intestinal stem cells.PLoS genetics · 2021Article
- The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(6;11).Oncogene · 2021Article
- Histone methylation in pancreatic cancer and its clinical implications.World journal of gastroenterology · 2021Review
- Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia.eLife · 2021Article
- SET1/MLL family of proteins: functions beyond histone methylation.Epigenetics · 2021Review
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Targeting methyltransferase PRMT5 retards the carcinogenesis and metastasis of HNSCC via epigenetically inhibiting Twist1 transcription.Neoplasia (New York, N.Y.) · 2020Article
- Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The MLL (mixed-lineage leukemia) proto-oncogene encodes a histone methyltransferase that creates the methylated histone H3K4 epigenetic marks, commonly associated with actively transcribed genes. In addition to its canonical histone methyltransferase SET domain, the MLL protein contains three plant homeodomain (PHD) fingers that are well conserved between species but whose potential roles and requirements for MLL function are unknown. Here, we demonstrate that the third PHD domain of MLL (PHD3) binds histone H3 trimethylated at lysine 4 (H3K4me3) with high affinity and specificity and H3K4me2 with 8-fold lower affinity. Biochemical and structural analyses using NMR and fluorescence spectroscopy identified key amino acids essential for the interaction with H3K4me3. Site-directed mutations of the residues involved in recognition of H3K4me3 compromised in vitro H3K4me3 binding but not in vivo localization of full-length MLL to chromatin sites in target promoters of MEIS1 and HOXA genes. Whereas intact PHD3 finger was necessary for MLL occupancy at these promoters, H3K4me3 binding was critical for MLL transcriptional activity. These results demonstrate that MLL occupancy and target gene activation can be functionally separated. Furthermore, these findings reveal that MLL not only "writes" the H3K4me3 mark but also binds the mark, and this binding is required for the transcriptional maintenance functions of MLL.
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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.