biostudies-literatureUnknown39(21-22)Yu HMammalian genomes undergo pervasive transcription in both genic and intergenic regions. Trimethylation of histone H3 lysine 4 (H3K4me3) is a deeply conserved and functionally important histone modification enriched at transcriptionally active promoters, where it facilitates RNA polymerase activity. H3K4me3 is also commonly found in intergenic regions, where its role is poorly understood. We interrogated the role of H3K4me3 at intergenic regulatory elements by using epigenetic editing to efficiently deposit H3K4me3 at intergenic loci. We found that H3K4me3 amplifies RNA polymerase activity and is actively remodeled at intergenic regions, shedding light on these important but poorly understood regions of the genome.Genes & development1290-1298https://www.ebi.ac.uk/biostudies/studies/S-EPMC12581817biostudies-literatureH3K4me3 amplifies transcription at intergenic active regulatory elements.PMC12581817Liao ZZhang YLesch BJWalters BWYu HfalseH3K4me3 amplifies transcription at intergenic active regulatory elements.Mammalian genomes undergo pervasive transcription in both genic and intergenic regions. Trimethylation of histone H3 lysine 4 (H3K4me3) is a deeply conserved and functionally important histone modification enriched at transcriptionally active promoters, where it facilitates RNA polymerase activity. H3K4me3 is also commonly found in intergenic regions, where its role is poorly understood. We interrogated the role of H3K4me3 at intergenic regulatory elements by using epigenetic editing to efficiently deposit H3K4me3 at intergenic loci. We found that H3K4me3 amplifies RNA polymerase activity and is actively remodeled at intergenic regions, shedding light on these important but poorly understood regions of the genome.2025-01-01T00:00:00Z2025 Nov2026-06-05T11:56:59.518Z2026-05-16T03:13:29.5ZS-EPMC125818174082566610.1101/gad.352841.125