Histone Modification  (组蛋白修饰)

Histone modifications are able to alter chromatin structure and are associated with both transcriptional activation and inhibition. Histone modifications can either activate or silence genes expression, depending on the residues added to the targeted histones and the extent of the modification. There are various kinds of histone modifications, including acetylation, methylation, citrullination, deamination, ubiquitination, ADP-ribosylation.

Histone acetylation, one of the most widely studied epigenetic modifications, usually occurs on basic amino acids (lysine and arginine). In general, acetylation activates gene expression by reducing the affinity of histones to DNA. Histone acetylation is transfered by histone acetyl transferases (HATs) and removed by histone deacetyltransferases (HDACs). HATs can be grouped into at least five different subfamilies, including HAT1 (KAT1), Gcn5/PCAF (KAT2a/KAT2B), MYST (KAT5), CBP/p300 (KAT3B/KAT3A), and Rtt109 (KAT11). CBP/p300 contains a bromodomain that is important in binding to chromatin, and has attracted widespread concern as promising epigenetic targets for diverse human diseases, including inflammation, cancer, autoimmune disorders, and cardiovascular disease.

Methylation is another widely studied histone modification, which is catalyzed by histone methyltransferases. Histone methylation can either activate or silence gene expression. For example, trimethylation of lysine 4 on H3 (H3K4me3) activates gene expression, while trimethylation of lysine 27 on H3 (H3K27me3) is reported to be associated with gene silencing. Histone demethylation is performed by two classes of histone demethylases: lysine-specific demethylase (LSD) family proteins (LSD1 and LSD2) and JmjC domain-containing histone demethylase (JHDM).

Other histone modifications are relatively rare, including histone deamination/citrullination, ubiquitination, ADP-ribosylation, deamination, N6-formylation, and O-GlcNAylation. For example, ADP-ribosylation of lysine residues occurs in less than 1% of histone proteins, but is observed particularly in the case of single DNA strand breaks.