H3K4me1
H3K4me1 is an
Nomenclature
H3K4me1 indicates monomethylation of lysine 4 on histone H3 protein subunit: [1]
Abbr. | Meaning |
H3 | H3 family of histones |
K | standard abbreviation for lysine |
4 | position of amino acid residue
(counting from N-terminus) |
me | methyl group |
1 | number of methyl groups added |
Lysine methylation
This diagram shows the progressive methylation of a lysine residue. The mono-methylation (second from left) denotes the methylation present in H3K4me1.
Understanding histone modifications
The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as
Mechanism and function of modification
H3K4me1 is enriched at active and primed enhancers.[4] Transcriptional enhancers control the cell-identity gene expression and are important in the cell identity. Enhancers are primed by histone H3K4 mono-/di-methyltransferase MLL4 and then are activated by histone H3K27 acetyltransferase p300.[5] H3K4me1 fine-tunes the enhancer activity and function rather than controls.[4] H3K4me1 is put down by KMT2C (MLL3) and KMT2D (MLL4)[6]
Marks associated with active gene transcription like H3K4me1 and H3K9me1 have very short half-lives.[8]
H3K4me1 with MLL3/4 can also act at promoters and repress genes.[8]
Relationship with other modifications
H3K4me1 is a chromatin signature of enhancers, H3K4me2 is highest toward the
Enhancers that have two opposing marks like the active mark H3K4me1 and repressive mark H3K27me3 at the same time are called bivalent or poised. These bivalent enhancers convert and become enriched with H3K4me1 and acetylated H3K27 (H3K27ac) after differentiation.[8]
Epigenetic implications
The post-translational modification of histone tails by either histone modifying complexes or chromatin remodelling complexes are interpreted by the cell and lead to complex, combinatorial transcriptional output. It is thought that a Histone code dictates the expression of genes by a complex interaction between the histones in a particular region.[9] The current understanding and interpretation of histones comes from two large scale projects: ENCODE and the Epigenomic roadmap.[10] The purpose of the epigenomic study was to investigate epigenetic changes across the entire genome. This led to chromatin states which define genomic regions by grouping the interactions of different proteins and/or histone modifications together. Chromatin states were investigated in Drosophila cells by looking at the binding location of proteins in the genome. Use of
- H3K4me1- primed enhancers
- H3K4me3-promoters
- H3K36me3-gene bodies
- H3K27me3-polycomb repression
- H3K9me3-heterochromatin
The human genome was annotated with chromatin states. These annotated states can be used as new ways to annotate a genome independently of the underlying genome sequence. This independence from the DNA sequence enforces the epigenetic nature of histone modifications. Chromatin states are also useful in identifying regulatory elements that have no defined sequence, such as enhancers. This additional level of annotation allows for a deeper understanding of cell specific gene regulation.[14]
Clinical significance
Suppression of the H3K4 mono- and di-demethylase LSD-1 might extend lifespan in various species.[15]
H3K4me allows binding of MDB and increased activity of DNMT1 which could give rise to CpG island methylator phenotype (CIMP). CIMP is a type of colorectal cancers caused by the inactivation of many tumor suppressor genes from epigenetic effects.[16]
Methods
The histone mark H3K4me1 can be detected in a variety of ways:
1. Chromatin Immunoprecipitation Sequencing (
2. Micrococcal Nuclease sequencing (MNase-seq) is used to investigate regions that are bound by well positioned nucleosomes. Use of the micrococcal nuclease enzyme is employed to identify nucleosome positioning. Well positioned nucleosomes are seen to have enrichment of sequences.[18]
3. Assay for transposase accessible chromatin sequencing (
See also
References
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- ^ "Whole-Genome Chromatin IP Sequencing (ChIP-Seq)" (PDF). Illumina. Retrieved 23 October 2019.
- ^ "MAINE-Seq/Mnase-Seq". illumina. Retrieved 23 October 2019.
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