H3K4me1 is an epigenetic modification of the DNA packaging protein histone H3. It is a marker that indicates monomethylation of the 4th lysine residue of histone H3 protein and is usually associated with gene enhancers.
H3K4me1 is enriched in activity enhancers and priming enhancers. Transcription enhancers control the expression of cell identity genes and are important for cell identity. The enhancer is initiated by the histone H3K4 mono/dimethyltransferase MLL4 and then activated by the histone H3K27 acetyltransferase p300. H3K4me1 can adjust enhancer activities and functions, not control. H3K4me1 is demethylated by KMT2C(MLL3) and KMT2D(MLL4), and LSD1 and the related LSD2/KDM1B demethylate H3K4me1 and H3K4me2. Markers associated with active gene transcription, such as H3K4me1 and H3K9me1, have very short half-lives. H3K4me1 with MLL3/4 can also act on promoters and repress genes.
H3K4me1 is a chromatin feature of enhancers, and H3K4me2 is highest at the 5' end of transcribed genes. H3K4me3 is highly enriched in promoter and balance genes. H3K27me3, H4K20me1, and H3K4me1 silence transcription in embryonic fibroblasts, macrophages, and human embryonic stem cells (ESCs). Enhancers with two opposite markers at the same time, such as the active marker H3K4me1 and the inhibitory marker H3K27me3, are called bivalent or balanced. These bivalent enhancers are transformed and enriched for H3K4me1 and acetylated H3K27 (H3K27ac) after differentiation.
Post-translational modifications to histone tails, by histone modification complexes, or chromatin remodeling complexes, can be interpreted by cells and lead to complex combinatorial transcriptional output. The histone code is thought to determine gene expression through complex interactions between histones in specific regions. The current understanding and interpretation of histones comes from two large projects: ENCODE and the Epigenomic Roadmap. A study of the obtained data led to the definition of chromatin states based on histone modifications. Some modifications were mapped and enrichments were found to localize to certain genomic regions. They also identified five core histone modifications, each associated with various cellular functions: H3K4me1 primer enhancer, H3K4me3 promoter H3K36me3 gene body, H3K27me3 polycomb repressor, and H3K9me3 heterochromatin.
The human genome is annotated with chromatin states. These annotation states can be used as new ways to annotate the genome independently of the underlying genome sequence. This independence from DNA sequence reinforces the epigenetic nature of histone modifications. Chromatin state can also be used to identify regulatory elements without defined sequences, such as enhancers. This additional level of annotation provides greater insight into cell-specific gene regulation.