H3K4me2

H3K4me2, or histone H3 lysine 4 dimethylation, is a post-translational modification where two methyl groups are added to the lysine 4 residue of histone H3. It is part of the histone code that regulates chromatin structure and gene expression.

Writers and erasers: The addition of the second methyl group to H3K4 is carried out by SET domain-containing methyltransferase complexes, notably the COMPASS-like complexes associated with proteins such as SETD1A, SETD1B and the KMT2A-D (MLL1-4) family. These complexes often work with core subunits like ASH2L, WDR5, RBBP5, and DPY-30. Demethylation of H3K4me2 can be performed by histone demethylases such as KDM1A/LSD1 (which also targets H3K4me1) and the KDM5/JARID1 family, which can remove di- and tri-methyl marks. Various reader proteins with domains such as PHD fingers recognize methylated lysines and help recruit downstream transcriptional machinery.

Genomic distribution and function: H3K4me2 is commonly enriched at promoter regions of actively transcribed genes and at certain enhancers, reflecting an association with transcriptional activity. It is often found at gene promoters that are actively initiating transcription or poised for transcription, and it can mark broader promoter regions compared to H3K4me3. The mark is dynamic and changes during development and differentiation, contributing to the regulation of gene expression by modulating chromatin accessibility and the recruitment of transcriptional regulators.

Detection and relevance: H3K4me2 is routinely detected by chromatin immunoprecipitation followed by sequencing (ChIP-seq) and is used in chromatin-state analyses to define regulatory regions. Abnormal patterns of H3K4me2 have been observed in various diseases, including cancer, where the activity of the responsible methyltransferases or demethylases may be altered.