Chromatin-modifying enzymes as therapeutic targets--Part 1.

, and . Expert Opin Ther Targets 12 (10): 1301-1312 (October 2008)


BACKGROUND: Disease pathogenesis may result from genetic alterations and/or a more diverse group of epigenetic changes. While events such as DNA methylation are well established, there is significant interest in nucleosome remodeling, RNA interference and histone modifications, as mechanisms that underlie epigenetic effects. While genetic mutations are permanent, epigenetic changes can be transitory. The potential to reverse epigenetic changes has led to the development of therapeutic strategies targeting chromatin-modifying enzymes. OBJECTIVE: To review the roles of chromatin-modifying enzymes in gene regulation and to highlight their potentials as therapeutic targets. Methods: This review is based on recently published literature and online resources. RESULTS/CONCLUSION: This paper focuses on enzymes responsible for histone acetylation, deacetylation, methylation and demethylation, and their potential as targets for epigenetic therapies. A subsequent paper will do the same for enzymes responsible for histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation as well as ATP-dependent nucleosome remodeling.

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