H3K4me3

H3K4me3 is an epigenetic chemical modification involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein. H3 is used to package DNA in eukaryotic cells (including human cells), and modifications to the histone alter the accessibility of genes for transcription. H3K4me3 is commonly associated with the activation of transcription of nearby genes. H3K4 trimethylation regulates gene expression through chromatin remodeling by the NURF complex. In bivalent chromatin, H3K4me3 is co-localized with the repressive modification H3K27me3 to control gene regulation. H3K4me3 also plays an important role in the genetic regulation of stem cell potency and lineage. H3K4me3 is an epigenetic chemical modification involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein. H3 is used to package DNA in eukaryotic cells (including human cells), and modifications to the histone alter the accessibility of genes for transcription. H3K4me3 is commonly associated with the activation of transcription of nearby genes. H3K4 trimethylation regulates gene expression through chromatin remodeling by the NURF complex. In bivalent chromatin, H3K4me3 is co-localized with the repressive modification H3K27me3 to control gene regulation. H3K4me3 also plays an important role in the genetic regulation of stem cell potency and lineage. The H3K4me3 modification is created by a lysine-specific histone methyltransferase (HMT) transferring three methyl groups to histone H3. H3K4me3 is methylated by methyltransferase complexes containing a protein WDR5, which contains the WD40 repeat protein motif. WDR5 associates specifically with dimethylated H3K4 and allows further methylation by methyltransferases, allowing for the creation and readout of the H3K4me3 modification. WDR5 activity has been shown to be required for developmental genes, like the Hox genes, that are regulated by histone methylation. H3K4me3 is a commonly used histone modification. H3K4me3 is one of the least abundant histone modifications; however, it is highly enriched at active promoters near transcription start sites (TSS) and positively correlated with transcription. H3K4me3 is used as a histone code or histone mark in epigenetic studies (usually identified through chromatin immunoprecipitation) to identify active gene promoters. H3K4me3 promotes gene activation through the action of the NURF complex, a protein complex that acts through the PHD finger protein motif to remodel chromatin. This makes the DNA in the chromatin accessible for transcription factors, allowing the genes to be transcribed and expressed in the cell. Regulation of gene expression through H3K4me3 plays a significant role in stem cell fate determination and early embryo development. Pluripotent cells have distinctive patterns of methylation that can be identified through ChIP-seq, permitting the identification of pluripotent cells. This is important in the development of induced pluripotent stem cells, in which one of the indicators of successful pluripotency induction is through comparing the epigenetic pattern to that of embryonic stem cells. In embryonic cells, H3K4me3 is part of a system of bivalent chromatin, in which regions of DNA are simultaneously marked with activating and repressing histone methylations. This is believed to allow for a flexible system of gene expression, in which genes are primarily repressed, but due to the presence of H3K4me3, may be expressed quickly as the cell progresses through development. These regions tend to coincide with transcription factor genes expressed at low levels. Some of these factors, such as the Hox genes, are essential for control development and cellular differentiation during embryogenesis. H3K4me3 is present at sites of DNA double-strand breaks where it promotes repair by the non-homologous end joining pathway.