View source for H3K36me

{{short description|Epigenetic modification}}
'''H3K36me''' is an [[epigenetic]] modification to the DNA packaging protein [[Histone H3]], specifically, the mono-[[methylation]] at the 36th [[lysine]] residue of the histone H3 protein.
There are diverse modifications at H3K36, such as phosphorylation, methylation, acetylation, and ubiquitylation, which have many important biological processes.<ref name=":0">{{cite journal | vauthors = Wagner EJ, Carpenter PB | title = Understanding the language of Lys36 methylation at histone H3 | journal = Nature Reviews. Molecular Cell Biology | volume = 13 | issue = 2 | pages = 115–26 | date = January 2012 | pmid = 22266761 | pmc = 3969746 | doi = 10.1038/nrm3274 }}</ref> The methylation of H3K36 has particularly had effects in transcriptional repression, alternative splicing, dosage compensation, DNA replication and repair, DNA methylation, and the transmission of the memory of gene expression from parents to offspring during development.<ref name=":0" />
== Nomenclature ==
H3K36me2 indicates [[Methylation|dimethylation]] of [[lysine]] 36 on histone H3 protein subunit:<ref>{{cite book | vauthors = Blakey CA, Litt MD | chapter = Chapter 2 - Histone modifications—models and mechanisms | veditors = Huang S, Litt MD, Blakey CA |title=Epigenetic Gene Expression and Regulation | location = London | publisher = Elsevier/Academic Press |date=2015-11-30  |pages=21–38 | doi = 10.1016/B978-0-12-799958-6.00002-0 |isbn=978-0-12-799958-6 }}</ref>
{| class="wikitable"
|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
|-
|1
|number of methyl groups added
|}
== Lysine methylation ==
:[[File:Methylation of lysine.svg|600px|Methylation-lysine]]
This diagram shows the progressive methylation of a lysine residue. The mono-methylation (second from left) denotes the methylation present in H3K36me1.
Lysine methylation is the addition of a methyl group to the lysine of histone proteins.<ref name=":1">{{cite journal | vauthors = Wang Z, Liu H | title = Lysine methylation regulates nervous system diseases | journal = Neuropeptides | volume = 76 | pages = 101929 | date = August 2019 | pmid = 31076097 | doi = 10.1016/j.npep.2019.04.004 | s2cid = 140312035 | url = http://www.sciencedirect.com/science/article/pii/S0143417918301574 }}</ref> This occurs via histone lysine methyltransferase (HMTase) that utilize ''S''-adenosylmethionine to specifically place the methyl group on histone Lys or Arg residues.<ref name=":0" /> So far, there have only been eight specific mammalian enzymes discovered that can methylate H3K36 in vitro and/or in vivo, all of which have identical catalytic SET domains but, different preferences for Lys36 residues in different methylation states.<ref name=":0" />
== Histone modifications ==
The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as [[histones]]. The complexes formed by the looping of the DNA are known as [[chromatin]]. The basic structural unit of chromatin is the [[nucleosome]], which consists of the core octamer of histones ([[Histone H2A|H2A]], [[Histone H2B|H2B]], [[Histone H3|H3]], and [[Histone H4|H4]]) as well as a linker histone and about 180 base pairs of DNA wrapped around it. These core histones are rich in lysine and arginine residues. The carboxyl (C) terminal end of these histones contribute to histone-histone interactions, as well as histone-DNA interactions. The amino (N) terminal charged tails are the site of the post-translational modifications, such as the one seen in H3K36me3.<ref>{{cite journal | vauthors = Ruthenburg AJ, Li H, Patel DJ, Allis CD | title = Multivalent engagement of chromatin modifications by linked binding modules | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 12 | pages = 983–94 | date = December 2007 | pmid = 18037899 | pmc = 4690530 | doi = 10.1038/nrm2298 }}</ref><ref>{{cite journal | vauthors = Kouzarides T | title = Chromatin modifications and their function | journal = Cell | volume = 128 | issue = 4 | pages = 693–705 | date = February 2007 | pmid = 17320507 | doi = 10.1016/j.cell.2007.02.005 | doi-access = free }}</ref>
== Epigenetic implications ==
The post-translational modification of histone tails by either histone-modifying complexes or chromatin remodeling complexes is interpreted by the cell and leads to the 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.<ref>{{cite journal | vauthors = Jenuwein T, Allis CD | title = Translating the histone code | journal = Science | volume = 293 | issue = 5532 | pages = 1074–80 | date = August 2001 | pmid = 11498575 | doi = 10.1126/science.1063127 | s2cid = 1883924 }}</ref> The current understanding and interpretation of histones come from two large scale projects: [[ENCODE]] and the Epigenomic roadmap.<ref>{{cite journal|authorlink2=John Stamatoyannopoulos| vauthors = Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, etal | collaboration = ENCODE Project Consortium | title = Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project | journal = Nature | volume = 447 | issue = 7146 | pages = 799–816 | date = June 2007 | pmid = 17571346 | pmc = 2212820 | doi = 10.1038/nature05874 | bibcode = 2007Natur.447..799B }}</ref> 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 melanogaster|Drosophila]] cells by looking at the binding location of proteins in the genome. The use of [[ChIP-sequencing]] revealed regions in the genome characterized by different banding.<ref>{{cite journal | vauthors = Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, Ward LD, Brugman W, de Castro IJ, Kerkhoven RM, Bussemaker HJ, van Steensel B | display-authors = 6 | title = Systematic protein location mapping reveals five principal chromatin types in Drosophila cells | journal = Cell | volume = 143 | issue = 2 | pages = 212–24 | date = October 2010 | pmid = 20888037 | pmc = 3119929 | doi = 10.1016/j.cell.2010.09.009 }}</ref> Different developmental stages were profiled in Drosophila as well, an emphasis was placed on histone modification relevance.<ref>{{cite journal | vauthors = Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, etal | collaboration = modENCODE Consortium | title = Identification of functional elements and regulatory circuits by Drosophila modENCODE | journal = Science | volume = 330 | issue = 6012 | pages = 1787–97 | date = December 2010 | pmid = 21177974 | pmc = 3192495 | doi = 10.1126/science.1198374 | bibcode = 2010Sci...330.1787R }}</ref> A look into the data obtained led to the definition of chromatin states based on histone modifications.<ref>{{cite journal | vauthors = Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, Linder-Basso D, Plachetka A, Shanower G, Tolstorukov MY, Luquette LJ, Xi R, Jung YL, Park RW, Bishop EP, Canfield TK, Sandstrom R, Thurman RE, MacAlpine DM, Stamatoyannopoulos JA, Kellis M, Elgin SC, Kuroda MI, Pirrotta V, Karpen GH, Park PJ | display-authors = 6 | title = Comprehensive analysis of the chromatin landscape in Drosophila melanogaster | journal = Nature | volume = 471 | issue = 7339 | pages = 480–5 | date = March 2011 | pmid = 21179089 | pmc = 3109908 | doi = 10.1038/nature09725 | bibcode = 2011Natur.471..480K }}</ref> Certain modifications were mapped and enrichment was seen to localize in certain genomic regions. Five core histone modifications were found with each respective one being linked to various cell functions.
* [[H3K4me3]]-promoters
* [[H3K4me1]]- primed enhancers
* H3K36me3-gene bodies
* [[H3K27me3]]-[[Polycomb-group proteins|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.<ref>{{cite journal | vauthors = Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, etal | collaboration = Roadmap Epigenomics Consortium | title = Integrative analysis of 111 reference human epigenomes | journal = Nature | volume = 518 | issue = 7539 | pages = 317–30 | date = February 2015 | pmid = 25693563 | pmc = 4530010 | doi = 10.1038/nature14248 | bibcode = 2015Natur.518..317. }}</ref>
== Methods ==
The histone mark H3K36me can be detected in a variety of ways:
# 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.<ref>[https://www.illumina.com/Documents/products/datasheets/datasheet_chip_sequence.pdf "Whole-Genome Chromatin IP Sequencing (ChIP-Seq)"](PDF). ''Illumina''. Retrieved 23 October 2019.</ref>
# Micrococcal Nuclease sequencing (MNase-seq) is used to investigate regions that are bound by well-positioned nucleosomes. The use of the micrococcal nuclease enzyme is employed to identify nucleosome positioning. Well-positioned [[Nucleosome|nucleosomes]] are seen to have enrichment of sequences.<ref>[https://www.illumina.com/science/sequencing-method-explorer/kits-and-arrays/maine-seq-mnase-seq-nucleo-seq.html?langsel=/us/ "MAINE-Seq/Mnase-Seq"]. ''illumina''. Retrieved 23 October 2019.</ref>
# Assay for transposase accessible chromatin sequencing (ATAC-seq) is used to look into regions that are nucleosome-free (open chromatin). It uses hyperactive [[Tn5 transposon]] to highlight nucleosome localization.<ref>{{cite journal | vauthors = Buenrostro JD, Wu B, Chang HY, Greenleaf WJ | title = ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide | journal = Current Protocols in Molecular Biology | volume = 109 | issue = 1 | pages = 21.29.1–21.29.9 | date = January 2015 | pmid = 25559105 | pmc = 4374986 | doi = 10.1002/0471142727.mb2129s109 }}</ref><ref>{{cite journal | vauthors = Schep AN, Buenrostro JD, Denny SK, Schwartz K, Sherlock G, Greenleaf WJ | title = Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions | journal = Genome Research | volume = 25 | issue = 11 | pages = 1757–70 | date = November 2015 | pmid = 26314830 | pmc = 4617971 | doi = 10.1101/gr.192294.115 }}</ref><ref>{{cite journal | vauthors = Song L, Crawford GE | title = DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells | journal = Cold Spring Harbor Protocols | volume = 2010 | issue = 2 | pages = pdb.prot5384 | date = February 2010 | pmid = 20150147 | pmc = 3627383 | doi = 10.1101/pdb.prot5384 }}</ref>
== See also ==
* [[Histone methylation]]
* [[Histone methyltransferase]]
* [[Methyllysine]]
== References ==
{{Reflist}}
[[Category:Methylation]]
[[Category:Epigenetics]]
[[Category:Post-translational modification]]