Editing Histone (section)

=== Chemistry ===

==== Lysine methylation ====
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[[File:methyl lysine.svg|thumb|300px]]

The addition of one, two, or many methyl groups to lysine has little effect on the chemistry of the histone; methylation leaves the charge of the lysine intact and adds a minimal number of atoms so steric interactions are mostly unaffected. However, proteins containing Tudor, chromo or PHD domains, amongst others, can recognise lysine methylation with exquisite sensitivity and differentiate mono, di and tri-methyl lysine, to the extent that, for some lysines (e.g.: H4K20) mono, di and tri-methylation appear to have different meanings. Because of this, lysine methylation tends to be a very informative mark and dominates the known histone modification functions.
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==== Glutamine serotonylation ====
Recently it has been shown, that the addition of a [[serotonin]] group to the position 5 glutamine of H3, happens in serotonergic cells such as neurons. This is part of the differentiation of the serotonergic cells. This post-translational modification happens in conjunction with the H3K4me3 modification. The serotonylation potentiates the binding of the general transcription factor [[Transcription factor II D|TFIID]] to the [[TATA box]].<ref>{{cite journal | vauthors = Farrelly LA, Thompson RE, Zhao S, Lepack AE, Lyu Y, Bhanu NV, Zhang B, Loh YE, Ramakrishnan A, Vadodaria KC, Heard KJ, Erikson G, Nakadai T, Bastle RM, Lukasak BJ, Zebroski H, Alenina N, Bader M, Berton O, Roeder RG, Molina H, Gage FH, Shen L, Garcia BA, Li H, Muir TW, Maze I | title = Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3 | journal = Nature | volume = 567 | issue = 7749 | pages = 535–539 | date = March 2019 | pmid = 30867594 | pmc = 6557285 | doi = 10.1038/s41586-019-1024-7 | bibcode = 2019Natur.567..535F }}</ref>

==== Arginine methylation ====
[[File:methyl arginine.svg|thumb|350px]]

What was said above of the chemistry of lysine methylation also applies to arginine methylation, and some protein domains—e.g., Tudor domains—can be specific for methyl arginine instead of methyl lysine. Arginine is known to be mono- or di-methylated, and methylation can be symmetric or asymmetric, potentially with different meanings.

==== Arginine citrullination ====
Enzymes called [[Protein-arginine deiminase|peptidylarginine deiminases]] (PADs) hydrolyze the imine group of arginines and attach a keto group, so that there is one less positive charge on the amino acid residue. This process has been involved in the activation of gene expression by making the modified histones less tightly bound to DNA and thus making the chromatin more accessible.<ref>{{cite journal | vauthors = Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JC, Zernicka-Goetz M, Nielsen ML, Gurdon JB, Kouzarides T | title = Citrullination regulates pluripotency and histone H1 binding to chromatin | journal = Nature | volume = 507 | issue = 7490 | pages = 104–8 | date = March 2014 | pmid = 24463520 | pmc = 4843970 | doi = 10.1038/nature12942 | url = https://www.repository.cam.ac.uk/handle/1810/254537 | bibcode = 2014Natur.507..104C }}</ref> PADs can also produce the opposite effect by removing or inhibiting mono-methylation of arginine residues on histones and thus antagonizing the positive effect arginine methylation has on transcriptional activity.<ref>{{cite journal | vauthors = Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T | title = Histone deimination antagonizes arginine methylation | journal = Cell | volume = 118 | issue = 5 | pages = 545–53 | date = September 2004 | pmid = 15339660 | doi = 10.1016/j.cell.2004.08.020 | doi-access = free }}</ref>

==== Lysine acetylation ====
[[File:acetyl lysine.tif|thumb|150px]]

Addition of an acetyl group has a major chemical effect on lysine as it neutralises the positive charge. This reduces electrostatic attraction between the histone and the negatively charged DNA backbone, loosening the chromatin structure; highly acetylated histones form more accessible chromatin and tend to be associated with active transcription. Lysine acetylation appears to be less precise in meaning than methylation, in that histone acetyltransferases tend to act on more than one lysine; presumably this reflects the need to alter multiple lysines to have a significant effect on chromatin structure. The modification includes [[H3K27ac]].
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==== Serine/threonine/tyrosine phosphorylation ====
[[File:amino acid phosphorylations.tif|thumb|400px]]

Addition of a negatively charged phosphate group can lead to major changes in protein structure, leading to the well-characterised role of [[phosphorylation]] in controlling protein function. It is not clear what structural implications histone phosphorylation has, but histone phosphorylation has clear functions as a post-translational modification, and binding domains such as BRCT have been characterised.