Histone code: Difference between revisions

Revision as of 21:42, 9 May 2017

Revision as of 23:14, 2 February 2018

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*[[Methylation]]

Both lysine and arginine residues are known to be methylated. Methylated lysines are the best understood marks of the histone code, as specific methylated lysine match well with gene expression states. Methylation of lysines H3K4 and H3K36 is correlated with transcriptional activation while demethylation of H3K4 is correlated with silencing of the genomic region. Methylation of lysines H3K9 and H3K27 is correlated with transcriptional repression.<ref name="Rosenfeld_2009">{{cite journal | last1 = Rosenfeld | first1 = Jeffrey A | last2 = Wang | first2 = Zhibin | last3 = Schones | first3 = Dustin | last4 = Zhao | first4=Keji | last5 = DeSalle | first5 = Rob | last6= Zhang | first6 = Michael Q | title = Determination of enriched histone modifications in non-genic portions of the human genome. | journal = BMC Genomics | volume = 10 | date = 31 March 2009 | pmid= 19335899 | doi = 10.1186/1471-2164-10-143 | pages = 143 | pmc = 2667539}}</ref> Particularly, H3K9me3 is highly correlated with constitutive heterochromatin.<ref name="Hublitz">{{cite journal | last1 = Hublitz | first1 = Philip | last2 = Albert | first2 = Mareike | last3 = Peters | first3 = Antoine | title = Mechanisms of Transcriptional Repression by Histone Lysine Methylation | journal = The International Journal of Developmental Biology | volume = 10 | issue = 1387 | pages = 335–354 | ___location = Basel | date = 28 April 2009 | issn =1696-3547}}</ref>

*[[Acetylation]] — by—by [[Histone acetyltransferase|HAT]] (histone acetyl transferase); deacetylation — bydeacetylation—by [[HDAC]] (histone deacetylase)

Acetylation tends to define the ‘openness’'openness' of [[chromatin]] as acetylated histones cannot pack as well together as deacetylated histones.

*[[Phosphorylation]]

*[[Ubiquitination]]

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* [[H3K122ac]] is enriched in poised promoters and also found in a different type of putative enhancer that lacks H3K27ac.

==Complexity of the histone code==

Unlike this simplified model, any real histone code has the potential to be massively complex; each of the four standard histones can be simultaneously modified at multiple different sites with multiple different modifications. To give an idea of this complexity, [[histone H3]] contains nineteen lysines known to be methylated — eachmethylated—each can be un-, mono-, di- or tri-methylated. If modifications are independent, this allows a potential 4¹⁹ or 280 billion different lysine methylation patterns, far more than the maximum number of histones in a human genome (6.4&nbsp;Gb / ~150&nbsp;bp = ~44 million histones if they are very tightly packed). And this does not include lysine acetylation (known for H3 at nine residues), arginine methylation (known for H3 at three residues) or threonine/serine/tyrosine phosphorylation (known for H3 at eight residues), not to mention modifications of other histones.

Every [[nucleosome]] in a cell can therefore have a different set of modifications, raising the question of whether common patterns of histone modifications exist. A recent study of about 40 histone modifications across human gene promoters found over 4000 different combinations used, over 3000 occurring at only a single promoter. However, patterns were discovered including a set of 17 histone modifications that are present together at over 3000 genes.<ref name="pmid18552846">{{cite journal |vauthors=Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, etal | title=Combinatorial patterns of histone acetylations and methylations in the human genome. | journal=Nat Genet | year= 2008 | volume= 40 | issue= 7 | pages= 897–903 | pmid=18552846 | doi=10.1038/ng.154 | pmc=2769248 }}</ref> Therefore, patterns of histone modifications do occur but they are very intricate, and we currently have detailed biochemical understanding of the importance of a relatively small number of modifications.

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==See also==

*[[Histone]]

*[[Histone-Modifyingmodifying Enzymesenzymes]]

==References==