H3K36me3
H3K36me3 is an
There are diverse modifications at H3K36 and have many important biological processes. H3K36 has different acetylation and methylation states with no similarity to each other.[1]
Nomenclature
H3K36me3 indicates trimethylation of lysine 36 on histone H3 protein subunit: [2]
Abbr. | Meaning |
H3 | H3 family of histones |
K | standard abbreviation for lysine |
36 | position of amino acid residue
(counting from N-terminus) |
me | methyl group |
3 | number of methyl groups added |
Lysine methylation
This diagram shows the progressive methylation of a lysine residue. The tri-methylation (right) denotes the methylation present in H3K36me3.
Understanding histone modifications
The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as
Mechanism and function of modification
Binding proteins
H3K36me3 can bind chromodomain proteins such as MSL3 hMRG15 and scEaf3.[5] It can bind PWWP proteins such as BRPF1 DNMT3A, HDGF2 and Tudor domains such as PHF19 and PHF1.[5]
DNA repair
H3K36me3 is required for homologous recombinational repair of DNA damage such as double-strand breaks.[6] The trimethylation is catalyzed by SETD2 methyltransferase.
Other roles
H3K36me3 acts as a mark for
Relationship with other modifications
H3K36me3 might define exons. Nucleosomes in the exons have more histone modifications such as H3K79, H4K20, and especially H3K36me3.[1]
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.[8] The current understanding and interpretation of histones comes from two large scale projects: ENCODE and the Epigenomic roadmap.[9] 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
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.[13]
Clinical significance
This histone methylation is responsible for maintaining gene expression stability. It is important throughout aging and has an impact on longevity. Genes that change their expression during aging have much lower levels of H3K36me3 in their gene bodies.[14]
There is reduced levels of H3K36me3 and
Methods
The histone mark H3K36me3 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.[17]
3. Assay for transposase accessible chromatin sequencing (ATAC-seq) is used to look in to regions that are nucleosome free (open chromatin). It uses hyperactive
See also
References
- ^ a b c "H3K36". epigenie. Retrieved 10 November 2019.
- ISBN 9780127999586.
- PMID 18037899.
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- ^ a b "Epigenetic modifications poster". Abcam. Retrieved 10 November 2019.
- PMID 24931610.
- PMID 21803857.
- S2CID 1883924.
- PMID 17571346.
- PMID 20888037.
- PMID 21177974.
- PMID 21179089.
- PMID 25693563.
- PMID 25838541.
- PMID 23533785.
- ^ "Whole-Genome Chromatin IP Sequencing (ChIP-Seq)" (PDF). Illumina. Retrieved 23 October 2019.
- ^ "MAINE-Seq/Mnase-Seq". illumina. Retrieved 23 October 2019.
- PMID 25559105.
- PMID 26314830.
- PMID 20150147.