School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
Curr Med Chem. 2013;20(2):167-85. doi: 10.2174/092986713804806667.
Epigenetics is defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence. The gene transcription is strictly correlated to chromatin structure, which could undergo covalent modifications of histones involving acetylation, methylation, phosphorylation and ubiquitination. Alterations in histones are implicated in many diseases, including cancer, by leading to tumor suppressor silencing or pro-apoptotic proteins downregulation. Although post-translational addition of methyl groups to the histone lysine has been discovered three decades ago, the importance of this epigenetic modification has emerged only in the last few years. Thenceforward histone methyltransferase inhibitors have been developed as potential therapeutic cancer agents. It should not be long before some selective inhibitors make their way into clinical trials. This review is mainly focused on the evolution in the development of new epigenetic modifier molecules modulating histone marks.
表观遗传学被定义为基因活性和表达的可遗传变化，这些变化发生在 DNA 序列没有改变的情况下。基因转录与染色质结构严格相关，染色质结构可以发生涉及乙酰化、甲基化、磷酸化和泛素化的组蛋白共价修饰。组蛋白的改变与许多疾病有关，包括癌症，通过导致肿瘤抑制因子沉默或促凋亡蛋白下调。尽管三十年前就发现了组蛋白赖氨酸上翻译后添加甲基基团，但这种表观遗传修饰的重要性仅在近几年才显现出来。此后，组蛋白甲基转移酶抑制剂已被开发为潜在的癌症治疗药物。一些选择性抑制剂进入临床试验应该不会太久。本文主要集中在开发新的表观遗传修饰分子以调节组蛋白标记方面的进展。
