Chromatin-modifying enzymes as therapeutic targets--Part 1.
Chromatin-modifying enzymes as therapeutic targets--Part 1.
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DOI：
10.1517/14728222.12.10.1301
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发表时间：
2008-10
影响因子：
5.8
通讯作者：
Archer TK
中科院分区：
文献类型：
--
作者：
Keppler BR;Archer TK
疾病的发病机制可能是由于遗传改变和/或更多样化的表观遗传变化。虽然DNA甲基化等事件已经得到了很好的建立，但核小体重塑、RNA干扰和组蛋白修饰作为表观遗传效应的基础机制也引起了人们的极大兴趣。虽然基因突变是永久性的，但表观遗传变化可能是暂时的。逆转表观遗传变化的潜力已经导致了靶向染色质修饰酶的治疗策略的发展。综述染色质修饰酶在基因调控中的作用，并探讨其作为治疗靶点的潜力。这篇综述是基于最近发表的文献和在线资源。本文重点介绍了负责组蛋白乙酰化、去乙酰化、甲基化和去甲基化的酶及其作为表观遗传治疗靶点的潜力。随后的论文将对负责组蛋白磷酸化、泛素化、SUMO化和聚ADP核糖基化以及ATP依赖性核小体重塑的酶进行同样的研究。
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. To review the roles of chromatin-modifying enzymes in gene regulation and to highlight their potentials as therapeutic targets. This review is based on recently published literature and online resources. 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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