ArticleNature genetics2023
MLL3/MLL4 methyltransferase activities control early embryonic development and embryonic stem cell differentiation in a lineage-selective manner.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 58 citations in OpenAlex.
- Weighted Single-Step GWAS Reveals Genetic Mechanisms Underlying Pregnancy Loss in Early Nellore Heifers.Animal genetics · 2026Article
- Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.Nature communications · 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
- 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
- Review
- A tryptophan-phenylalanine binding motif for the histone methyltransferases MLL4 and MLL3.The Journal of biological chemistry · 2026Article
- Histone acetylation and methylation in rare diseases: from molecular mechanisms to clinical presentations.Frontiers in cell and developmental biology · 2026Review
- Epigenetic remodeling during early embryonic development.Frontiers in cell and developmental biology · 2026Review
- CRISPR live-cell imaging reveals chromatin dynamics and enhancer interactions at multiple non-repetitive loci.Nature biotechnology · 2025Article
- Article
- Functional dissection of H3K4 methyltransferases reveals distinct catalytic and non-catalytic roles in C. elegans development.Development (Cambridge, England) · 2025Article
- Epigenetic control of cell identities from epiblast to gastrulation.The FEBS journal · 2025Review
- Article
- Histone lysine methyltransferases MLL3 and MLL4 direct gene expression to produce platelets efficiently.Nature communications · 2025Article
- Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.Cell reports · 2025Article
- Preliminary investigation of the epigenetic regulation of KMT2D via H3K4me1/H3K27ac in oral squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- Origin, fate and function of extraembryonic tissues during mammalian development.Nature reviews. Molecular cell biology · 2025Review
- Chromatin landscape at cis-regulatory elements orchestrates cell fate decisions in early embryogenesis.Nature communications · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
H3K4me1 methyltransferases MLL3 (KMT2C) and MLL4 (KMT2D) are critical for enhancer activation, cell differentiation and development. However, roles of MLL3/4 enzymatic activities and MLL3/4-mediated enhancer H3K4me1 in these processes remain unclear. Here we report that constitutive elimination of both MLL3 and MLL4 enzymatic activities prevents initiation of gastrulation and leads to early embryonic lethality in mice. However, selective elimination of MLL3/4 enzymatic activities in embryonic, but not extraembryonic, lineages leaves gastrulation largely intact. Consistent with this, embryonic stem cells (ESCs) lacking MLL3/4 enzymatic activities can differentiate toward the three embryonic germ layers but show aberrant differentiation to extraembryonic endoderm (ExEn) and trophectoderm. The failure in ExEn differentiation can be attributed to markedly reduced enhancer-binding of the lineage-determining transcription factor GATA6. Furthermore, we show that MLL3/4-catalyzed H3K4me1 is largely dispensable for enhancer activation during ESC differentiation. Together, our findings suggest a lineage-selective, but enhancer activation-independent, role of MLL3/4 methyltransferase activities in early embryonic development and ESC differentiation.
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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.