H3K4me3

H3K4me3 refers to the trimethylation of lysine 4 on histone H3. It is a histone modification strongly associated with active gene promoters and is typically enriched near transcription start sites, often at CpG-rich promoter regions. Genome-wide, H3K4me3 peaks are sharp at promoters and correlate with transcription initiation and RNA polymerase II engagement.

Biochemically, H3K4me3 is deposited by COMPASS-like methyltransferase complexes. In mammals, two major branches exist: SET1A/SET1B complexes and MLL1-MLL4 (KMT2A-D) complexes. These complexes share core subunits such as ASH2L, RBBP5, WDR5, and DPY-30, and they are recruited to promoters in coordination with the transcription machinery. Methylation states can be dynamic and are linked to transcriptional activity, often occurring in a co-transcriptional context.

Reader proteins containing plant homeodomain (PHD) fingers recognize H3K4me3 and help recruit transcriptional machinery and chromatin remodelers to promoters. Examples include TAF3 and members of the ING family. H3K4me3 typically functions in concert with other active marks, such as H3K27ac, to promote and stabilize transcriptional initiation.

Regulation and significance extend to demethylation and disease relevance. H3K4me3 levels are removed by demethylases in the KDM5 (JARID1) family, among others, contributing to dynamic control of promoter activity. Aberrant H3K4me3 patterns are associated with development, differentiation, and various diseases, including cancer. ChIP-seq and related methods map H3K4me3 to study transcriptional landscapes and promoter activity.