ArticleMolecular cell2017
Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.
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Who cites it
246 citing papers in PubMed, 408 citations in OpenAlex.
- A systematic single-cell analysis of enhancer RNAs across human and mouse.Nucleic acids research · 2026Article
- A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo.Science advances · 2026Article
- Identifying critical lysines in mammalian histone H3 with high-throughput CRISPR prime editing.Nature genetics · 2026Article
- MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state.Blood · 2026Article
- UDP-glucuronate decarboxylase 1 promotes tumor immune evasion by accelerating KMT2D loss in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers.Nature communications · 2026Article
- HPL-2/HP1 and MET-2/SETDB1 bind distinct co-factors that promote heterochromatic foci, gene repression and organogenesis independently of H3K9 methylation.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of the MLL4 complex in H3K4 methylation and p53-dependent transcription activation.Molecular cell · 2026Article
- Enhancers integrate microenvironmental signals in muscle stem cells during regeneration in health, disease, and aging.Skeletal muscle · 2026Review
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation.The EMBO journal · 2026Article
- Dual role of ZIC2 during neural induction: from priming transcription factor to enhancer activator.Nucleic acids research · 2026Article
- MLL3/4 methyltransferases regulate the differentiation of pluripotent stem cells through coordinating glycolysis and mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of Hippo Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From chromosomal protein disorder to chromatin phase separation.Epigenetics & chromatin · 2026Review
- KMT2C and KMT2D amplify GRHL2-driven enhancer activation.bioRxiv : the preprint server for biology · 2026Article
- Chromatin loop proteomics finds a non-catalytic function for a histone demethylase.Nature genetics · 2026Article
- JMJD2 regulates enhancer-promoter interactions via biomolecular condensate formation.Nature genetics · 2026Article
- Deciphering the eRNA landscape and revealing target aberrant pathways in prostate cancer.BMC cancer · 2026Article
186 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Monomethylation of histone H3 at lysine 4 (H3K4me1) and acetylation of histone H3 at lysine 27 (H3K27ac) are correlated with transcriptionally engaged enhancer elements, but the functional impact of these modifications on enhancer activity is not well understood. Here we used CRISPR/Cas9 genome editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases. Loss of H3K4me1 from enhancers in Mll3/4 catalytically deficient cells causes partial reduction of H3K27ac, but has surprisingly minor effects on transcription from either enhancers or promoters. In contrast, loss of Mll3/4 proteins leads to strong depletion of enhancer Pol II occupancy and eRNA synthesis, concomitant with downregulation of target genes. Interestingly, downregulated genes exhibit reduced polymerase levels in gene bodies, but not at promoters, suggestive of pause-release defects. Altogether, our results suggest that enhancer H3K4me1 provides only a minor contribution to the long-range coactivator function of Mll3/4.
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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.