Histone modification targeting

Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14 R546-R551 Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276 36734-36741... 

It is currently believed that double-stranded break (DSB) repair enzymes may act as baits to attract invading T-DNA molecules to the sites of integration. This DSB repair machinery may be transported via histone modifications as part of a general process of intranuclear protein traffic that also allows transcriptional factors to reach their target promoters (Lacroix et al., 2006b). 

CpG islands of tumor-suppressor genes are hypermethylated in cancer cells. Therefore, they recmit multiple repressors that lead to a characteristic histone modification pattern the deacetylation of histones H3 and H4, the methylation of lysine 9 of histone H3, and the demethylation of lysine 4 of histone H3 (52). In addition, it has been shown that the polycomb protein EZH2 associates with DNMTs and that specific methylation of lysine 27 of histone H3 is required to establish DNA methylation in a subset of target genes (6). 

Chi P, Allis CD, Wang GG (2010) Covalent histone modifications—miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer 10 457 69 Herranz M, Esteller M (2006) New therapeutic targets in cancer the epigenetic connection. Clin Transl Oncol 8 242-249... 

The exact role of individual histone acetylations will have to be determined in the context of other modifications and the number of lysine residues effected. However, the general importance of histone acetylation as a regulator for chromatin activity is undisputed. This leads to the intriguing possibility to develop drugs that target histone acetylation for therapeutic purposes. The primary targets for drug development are the histone acetyl transferases (HATs) and the histone deacetylases (HDACs) which introduce and remove histone acetylations [2, 3]. 

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