Histone H3 lysine 4 trimethylation (H3K4me3) (H3K4me3)

Histone H3 lysine 4 trimethylation (H3K4me3) is a pivotal post-translational modification located at the N-terminal tail of histone H3, serving as a hallmark of transcriptionally active or poised gene promoters (Oncotarget, 2013). It plays a fundamental role in gene regulation by recruiting reader proteins, such as TFIID and chromatin remodelers, which facilitate the assembly of the transcription initiation complex and promote RNA polymerase II elongation (Trends in Cell Biology, 2024). The homeostasis of H3K4me3 is maintained by the opposing actions of writer enzymes, primarily the MLL/KMT2 family of methyltransferases, and eraser enzymes, such as the KDM5 family of demethylases (ResearchGate, 2022). Aberrant H3K4me3 patterns are strongly linked to the pathogenesis of various diseases, including mixed-lineage leukemia (MLL), where MLL rearrangements drive oncogenic gene expression, and solid tumors like breast and prostate cancer (NIH, 2021). Furthermore, dysregulation of this mark is implicated in neurodegenerative disorders such as Huntington's disease and in the regulation of immune cell plasticity (PLOS One, 2015; Frontiers, 2023). Therapeutic strategies targeting H3K4me3 involve small molecule inhibitors of its regulatory enzymes, such as MLL1-Menin inhibitors (e.g., Revumenib) and KDM5 inhibitors, which aim to restore normal epigenetic landscapes and suppress disease-associated transcriptional programs (BMJ, 2023).

Other names

H3K4me3Trimethylated histone H3 lysine 4Histone H3 trimethyl Lys4H3K4me3 mark

Modulation of H3K4me3 levels or recognition through the inhibition of histone methyltransferases (writers), histone demethylases (erasers), or reader proteins (PHD finger/chromodomain proteins).