With hundreds of PTMs now described for histones, you might imagine that the language that they combine to create is highly complex. However, as has been reviewed by Oliver Rando (Rando 2012), only a tiny proportion of the complexity is used in vivo, with the same combinations of chromatin marks occurring repeatedly in the genome. As Rando puts it (Rando 2012): “At present, an intellectual schism exists between biochemists on one hand, and geneticists and epigenomics researchers on the other. Genome-wide mapping of histone modifications invariably shows that histone modifica- tions occur in groups of multiple highly correlated modifications, demon- strating that the huge potential space of modification combinations is not utilized in vivo.” This lack of diversity argues against the idea that combi- nations of modifications mediate complexity in the regulation of gene ex- pression, although Rando also cites evidence for some readers that bind preferentially when a histone bears a specific combination of PTMs.
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