H3K9me2
H3K9me2 is an
Nomenclature
H3K9me2 indicates dimethylation of lysine 9 on histone H3 protein subunit:[21]
| Abbr. | Meaning |
| H3 | H3 family of histones |
| K | standard abbreviation for lysine |
| 9 | position of amino acid residue
(counting from N-terminus) |
| me | methyl group |
| 2 | number of methyl groups added |
Lysine methylation
This diagram shows the progressive methylation of a lysine residue. The di-methylation (third from left) denotes the methylation presentpresent in H3K9me2.
Understanding histone modifications
The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as
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.[24] The current understanding and interpretation of histones comes from two large scale projects: ENCODE and the Epigenomic roadmap.[25] 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
- H3K4me3-promoters
- H3K4me1- primed enhancers
- H3K36me3-gene bodies
- H3K27me3-polycomb repression
- H3K9me3-heterochromatin
- H3K9me2-facultative 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.[29]
Clinical significance
Addiction
Chronic addictive drug exposure results in
Friedreich's ataxia
Cardiovascular disease
H3K9me2 is present at a subset of
Methods
Histone modifications, including H3K9me2, can be detected using a variety of methods:
- Chromatin Immunoprecipitation Sequencing (ChIP-sequencing) measures the amount of DNA enrichment once bound to a targeted protein and immunoprecipitated. It results in good optimization and is used in vivo to reveal DNA-protein binding occurring in cells. ChIP-Seq can be used to identify and quantify various DNA fragments for different histone modifications along a genomic region.[37]
- CUT&RUN(Cleavage Under Targets and Release Using Nuclease). In CUT&RUN, targeted DNA-protein complexes are isolated directly from the cell nucleus rather than following a precipitation step. To perform CUT&RUN, a specific antibody to the DNA-binding protein of interest and ProtA-MNase is added to permeabilised cells. MNase is tethered to the protein of interest through the ProtA-antibody interaction and MNase cleaves the surrounding, unprotected DNA to release protein-DNA complexes, which can then be isolated and sequenced.[38][39] CUT&RUN is reported to give a much higher signal to noise ratio compared to traditional ChIP. CUT&RUN therefore requires one tenth of the sequencing depth of ChIP and permits genomic mapping of histone modifications and transcription factors using extremely low cell numbers.[40][38][39]
- Modification-specific intracellular antibody probes. Sensitive fluorescent genetically encoded histone modification-specific intracellular antibody (mintbody) probes can be used to monitor changes in histone modifications in living cells.[41]
See also
References
- ^ a b "H3K9me2". HIstome: The Histone Infobase. Retrieved 8 June 2018.
- ^
- ^ PMID 26472529.
Chronic social defeat stress decreases expression of G9a and GLP (G9a-like protein), two histone methyltransferases that catalyze the dimethylation of Lys9 of histone H3 (H3K9me2) (Covington et al., 2011), a mark associated with gene repression.
- PMID 17512414.
- PMID 18552846.
- ^ PMID 21498567.
- PMID 27052169.
- PMID 20037608.
- PMID 21725293.
- ^ PMID 19151716.
- PMID 19265653.
- ^ "Histone-lysine N-methyltransferase, H3 lysine-9 specific 3". HIstome: The Histone Infobase. Retrieved 8 June 2018.
- PMID 18451103.
- PMID 23105005.
- PMID 29281720.
- ^ PMID 31434493.
- PMID 22412156.
- ^ PMID 23643695.
- ^ PMID 23020045.
- ^ PMID 23475113.
- ISBN 9780127999586.
- PMID 18037899.
- PMID 17320507.
- S2CID 1883924.
- PMID 17571346.
- PMID 20888037.
- PMID 21177974.
- PMID 21179089.
- PMID 25693563.
- PMID 25409693.
- S2CID 19157711.
- PMID 27600412.
- S2CID 41075220.
- ^ PMID 28135625.
- PMID 21309809.
- PMID 31254285.
- ^ "Whole-Genome Chromatin IP Sequencing (ChIP-Seq)" (PDF). Illumina. Retrieved 23 October 2019.
- ^ PMID 28079019.
- ^ doi:10.1101/569129.
- PMID 30688406.
- PMID 23942372.