ArticleThe EMBO journal2025
Histone methyltransferases MLL2 and SETD1A/B play distinct roles in H3K4me3 deposition during the transition from totipotency to pluripotency.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Establishment of a Common Marmoset Lineage Carrying a Frameshift Mutation in SETD1A, a Schizophrenia Risk Gene.Journal of neurochemistry · 2026Article
- High-resolution mapping of embryonic genome activation unveils a decoupling of transcription activation from precocious H3K4me3 removal.Science advances · 2026Article
- Ythdf2/Setd1b regulatory axis is essential for cerebellar development through regulating epigenetic reprogramming.Molecular psychiatry · 2026Article
- Epigenetic deciphering of ovarian aging: multilayer interactive mechanisms and targeted reversal strategies.Epigenetics & chromatin · 2026Review
- Review
- Dynamic Balance of Histone H3 Methylation: Regulatory Mechanisms and Therapeutic Prospects in RA Immune Dysregulation and Bone Metabolism Imbalance.Journal of immunology research · 2026Review
- Epigenetic remodeling during early embryonic development.Frontiers in cell and developmental biology · 2026Review
- KMT2A-Mediated transcriptional regulation in stemness and cancer: molecular mechanisms and therapeutic opportunities.Medical oncology (Northwood, London, England) · 2025Review
- Canonical and Non-Canonical Functions of Histone H3K4 Methylation Modifiers in Cancer.Cancer science · 2025Review
- Broad H3K4me3 domains support oocyte genome silencing and maturation but are dispensable for repression in early embryos.Development (Cambridge, England) · 2025Article
- CRISPR Screening Reveals a Novel Role for FOXH1 in Regulating Pluripotency of Porcine Embryonic Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Nuclear Localization of ACLY Guards Early Embryo Development Through Recruiting P300 and HAT1 to Promote Histone Acetylation and Transcription.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.Histochemistry and cell biology · 2025Review
- Article
- FOXO4-SP6 axis controls surface epithelium commitment by mediating epigenomic remodeling.Stem cell reports · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
In early mammalian embryogenesis, a shift from non-canonical histone H3 lysine 4 trimethylation (H3K4me3) linked to transcriptional repression to canonical H3K4me3 indicating active promoters occurs during zygotic genome activation (ZGA). However, the mechanisms and roles of these H3K4me3 states in embryogenesis remain poorly understood. Our research reveals that the histone methyltransferase MLL2 is responsible for installing H3K4me3 (both non-canonical and canonical) in totipotent embryos, while a transition to SETD1A/B-deposited H3K4me3 occurs in pluripotent embryos. Interestingly, MLL2-mediated H3K4me3 operates independently of transcription, fostering a relaxed chromatin state conducive to totipotency rather than directly influencing transcription. Conversely, SETD1A/B-mediated H3K4me3, which depends on transcription, is crucial for facilitating expression of genes essential for pluripotency and pre-implantation development. Our findings highlight the role of the H3K4me3 transition, mediated by an MLL2-to-SETD1A/B relay mechanism, in the regulation of transition from totipotency to pluripotency during early embryogenesis.
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