Histone code: Difference between revisions

Revision as of 23:37, 3 December 2023

Latest revision as of 22:30, 1 April 2024

Line 103:

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—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 Gb / ~150 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.{{cn|date=March 2023}}

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 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[[Mass spectrometry]]-based [[top-down proteomics]] has provided more insight into these patterns by being able to discriminate single molecule co-occurrence from co-localization in the genome or on the same nucleosome.<ref name="Taylor">{{cite journal |vauthors=Taylor BC, Young NL |title=Combinations of histone post-translational modifications |journal=Biochemical Journal |volume=487 |issue=3 |pages=511–532 |date=10 Feb 2021 |pmid=33567070 |doi=10.1042/BCJ20200170}}</ref> A variety of approaches have been used to delve into detailed biochemical mechanisms that demonstrate the importance of interplay between histone modifications. Thus, specific patterns of histone modifications doare more common than others. These patterns are functionally occurimportant but they are very intricate, and wechallenging to study. We currently have detailedthe best biochemical understanding of the importance of a relatively small number of discrete modifications and a few combinations.

Structural determinants of histone recognition by readers, writers, and erasers of the histone code are revealed by a growing body of experimental data.<ref name="Wang">{{cite journal |vauthors=Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M |title=Structural Genomics of Histone Tail Recognition |journal=Bioinformatics |volume=26|issue=20 |pages=2629–2630 |date=24 Aug 2010 |pmid=20739309 |pmc=2951094 |doi=10.1093/bioinformatics/btq491}}</ref>

==See also==