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The KMT2F histone methyltransferase interacts with the RNA polymerase I machinery to promote ribosomal RNA transcription.

GSE261933 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2026/04/24 Platform GPL30173
Summary
Trimethylation of histone 3 lysine 4 (H3K4me3) is a mark of active transcription, and its regulatory role in RNA polymerase II-mediated transcription has been well-studied. However, if and how this mark regulates RNA polymerase I (RNA Pol I) is not known. Here, we used customized genome assemblies for rDNA to demonstrate that KMT2A and KMT2F bind to entire rDNA loci. The binding of these enzymes was mirrored by the binding of H3K4me2 and H3K4me3 marks. Using biochemical assays, we demonstrate the interaction of KMT2- specific subunits with RNA Pol I transcriptional machinery. Our findings reveal KMT2F as the primary KMT depositing the H3K4me3 on rDNA. Loss of H3K4me3 adversely affects the epigenetic landscape and leads to repression of the rDNA locus. Mechanistically, using mammalian cells as a model system, we demonstrate that KMT2F promotes the formation of the pre-initiation complex by RNA Pol I. Our findings highlight the thus far undiscovered role of H3K4me3 in the transcriptional initiation of rDNA genes.
Published in
The KMT2F histone methyltransferase interacts with the RNA polymerase I machinery to promote ribosomal RNA transcription
Lone KA, Karole AM, Ravindran G et al. · PLoS biology 2026 · PMID 42096476 · doi:10.1371/journal.pbio.3003785
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Also filed as BioProject PRJNA1089604 and SRA study SRP496469. Searching any of these in the dataset finder brings you back here.

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