ArticleNucleic acids research2020
H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- WDR5-H3K4me3 Epigenetic Axis Promotes TRMT6-Dependent tRNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neuron-specific WDR5 epigenetically upregulates ARID5B to impair GABAergic synaptic transmission and promotes epileptogenesis.Theranostics · 2026Article
- Mechanistic insights into the stimulation of the histone H3K9 methyltransferase Clr4 by proximal H3K14 ubiquitination.Science advances · 2025Article
- PRMT1-mediated methylation regulates MLL2 stability and gene expression.Nucleic acids research · 2025Article
- Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.Nature chemical biology · 2025Article
- Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Histone H2B ubiquitylation: Connections to transcription and effects on chromatin structure.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- Diverse modes of regulating methyltransferase activity by histone ubiquitination.Current opinion in structural biology · 2023Review
- Histone variant-specific post-translational modifications.Seminars in cell & developmental biology · 2023Review
- Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates.iScience · 2022Article
- Dual role of pseudogene TMEM198B in promoting lipid metabolism and immune escape of glioma cells.Oncogene · 2022Article
- Downregulation of SETD5 Suppresses the Tumorigenicity of Hepatocellular Carcinoma Cells.Molecules and cells · 2022Article
- DBC1 is a key positive regulator of enhancer epigenomic writers KMT2D and p300.Nucleic acids research · 2022Article
- Decoding histone ubiquitylation.Frontiers in cell and developmental biology · 2022Review
- New connections between ubiquitylation and methylation in the co-transcriptional histone modification network.Current genetics · 2021Review
- The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes.Clinical epigenetics · 2021Review
- Construction of a prognostic model with histone modification-related genes and identification of potential drugs in pancreatic cancer.Cancer cell international · 2021Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
In mammalian cells, distinct H3K4 methylation states are created by deposition of methyl groups by multiple complexes of histone lysine methyltransferase 2 (KMT2) family proteins. For comprehensive analyses that directly compare the catalytic properties of all six human KMT2 complexes, we employed a biochemically defined system reconstituted with recombinant KMT2 core complexes (KMT2CoreCs) containing minimal components required for nucleosomal H3K4 methylation activity. We found that each KMT2CoreC generates distinct states and different levels of H3K4 methylation, and except for MLL3 all are stimulated by H2Bub. Notably, SET1BCoreC exhibited the strongest H3K4 methylation activity and, to our surprise, did not require H2B ubiquitylation (H2Bub); in contrast, H2Bub was required for the H3K4me2/3 activity of the paralog SET1ACoreC. We also found that WDR5, RbBP5, ASH2L and DPY30 are required for efficient H3K4 methyltransferase activities of all KMT2CoreCs except MLL3, which could produce H3K4me1 in the absence of WDR5. Importantly, deletion of the PHD2 domain of CFP1 led to complete loss of the H3K4me2/3 activities of SET1A/BCoreCs in the presence of H2Bub, indicating a critical role for this domain in the H2Bub-stimulated H3K4 methylation. Collectively, our results suggest that each KMT2 complex methylates H3K4 through distinct mechanisms in which individual subunits differentially participate.
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