ArticleMolecular and cellular biology2013
The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4 monomethylases at enhancers.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers.
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Who cites it
286 citing papers in PubMed, 426 citations in OpenAlex.
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Deciphering the Molecular Landscape of Squamous Cell Carcinoma of the Anal Canal: From Biology to Precision Oncology.Cancers · 2026Review
- BAP1 and UTX are dispensable for transcription-driven Polycomb erasure but essential for enhancer establishment.The Journal of biological chemistry · 2026Article
- Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability.PLoS computational biology · 2026Article
- MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state.Blood · 2026Article
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- Histone lysine methyltransferases KMT2C and KMT2D join the all-star tumor suppressor team in gastrointestinal cancer.The Journal of clinical investigation · 2026Article
- UDP-glucuronate decarboxylase 1 promotes tumor immune evasion by accelerating KMT2D loss in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- H3K4 Methylation Readers in Plants: Recognition Mechanisms and Biological Functions.International journal of molecular sciences · 2026Review
- The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers.Nature communications · 2026Article
- Kdm6b-mediated epigenetic coordination of temporal precision during motor neuron differentiation.EMBO reports · 2026Article
- Deciphering the single-cell molecular landscape of ampullary cancer: A rare gastrointestinal malignancy.iScience · 2026Article
- Molecular mechanisms of the MLL4 complex in H3K4 methylation and p53-dependent transcription activation.Molecular cell · 2026Article
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- MLL3/4 methyltransferases regulate the differentiation of pluripotent stem cells through coordinating glycolysis and mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- KMT2C and KMT2D amplify GRHL2-driven enhancer activation.bioRxiv : the preprint server for biology · 2026Article
- The Histone Methyltransferase KMT2D Is a Critical Mediator of Lineage Plasticity and Therapeutic Response in Castration-Resistant Prostate Cancer.Cancer research · 2026Article
- A tryptophan-phenylalanine binding motif for the histone methyltransferases MLL4 and MLL3.The Journal of biological chemistry · 2026Article
- H3K4me1 directs H3K36me2 and H3K36me3 deposition in land plants.Nature communications · 2026Article
- Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability.bioRxiv : the preprint server for biology · 2026Article
226 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Histone H3 lysine 4 (H3K4) can be mono-, di-, and trimethylated by members of the COMPASS (complex of proteins associated with Set1) family from Saccharomyces cerevisiae to humans, and these modifications can be found at distinct regions of the genome. Monomethylation of histone H3K4 (H3K4me1) is relatively more enriched at metazoan enhancer regions compared to trimethylated histone H3K4 (H3K4me3), which is enriched at transcription start sites in all eukaryotes. Our recent studies of Drosophila melanogaster demonstrated that the Trithorax-related (Trr) branch of the COMPASS family regulates enhancer activity and is responsible for the implementation of H3K4me1 at these regions. There are six COMPASS family members in mammals, two of which, MLL3 (GeneID 58508) and MLL4 (GeneID 8085), are most closely related to Drosophila Trr. Here, we use chromatin immunoprecipitation-sequencing (ChIP-seq) of this class of COMPASS family members in both human HCT116 cells and mouse embryonic stem cells and find that MLL4 is preferentially found at enhancer regions. MLL3 and MLL4 are frequently mutated in cancer, and indeed, the widely used HCT116 cancer cell line contains inactivating mutations in the MLL3 gene. Using HCT116 cells in which MLL4 has also been knocked out, we demonstrate that MLL3 and MLL4 are major regulators of H3K4me1 in these cells, with the greatest loss of monomethylation at enhancer regions. Moreover, we find a redundant role between Mll3 (GeneID 231051) and Mll4 (GeneID 381022) in enhancer H3K4 monomethylation in mouse embryonic fibroblast (MEF) cells. These findings suggest that mammalian MLL3 and MLL4 function in the regulation of enhancer activity and that mutations of MLL3 and MLL4 that are found in cancers could exert their properties through malfunction of these Trr/MLL3/MLL4-specific (Trrific) enhancers.
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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.