In general, methylation on histone H3 lysine 4 (H3K4), H3K36, and H3K79 is linked to lively gene expression, whereas di- and tri-methylation on H3K9, H3K27, and H4K20 are associated with gene silencing. Although ∼80 enzymes have been shown to dynamically regulate histone lysine methylation, only some non-histone proteins have been reported as substrates of these enzymes. Most research of lysine methylation have focused on just a few target proteins via a candidate approach.

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