Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation

Research output: Contribution to journalResearch articleContributedpeer-review



Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) oocytes using ultra-low input ChIP-seq, with comparisons to DNA methylation and gene expression analyses. H3K4me3 was redistributed in Setd1b cKO oocytes showing losses at active gene promoters associated with downregulated gene expression. Remarkably, many regions also gained H3K4me3, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich, which are hallmarks of MLL2 targets. Consequently, loss of SETD1B disrupts the balance between MLL2 and de novo DNA methyltransferases in determining the epigenetic landscape during oogenesis. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression and MLL2 to CpG content.


Original languageEnglish
Pages (from-to)1993-2004
Number of pages12
JournalNucleic acids research
Issue number4
Publication statusPublished - 28 Feb 2022

External IDs

PubMedCentral PMC8887468
Scopus 85125552487
unpaywall 10.1093/nar/gkac051
ORCID /0000-0002-7481-0220/work/142247413
ORCID /0000-0002-4754-1707/work/142248080



  • Animals, CpG Islands/genetics, DNA Methylation, Histone Methyltransferases/genetics, Histones/genetics, Lysine/metabolism, Mammals/genetics, Oogenesis/genetics

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