书写和重写癌细胞的表观遗传密码：从工程蛋白到小分子。
Writing and rewriting the epigenetic code of cancer cells: from engineered proteins to small molecules.
机构信息
School of Anatomy, Physiology, and Human Biology, M309, the University of Western Australia, 35 Stirling Highway, Crawley, 6009, WA, Australia.
出版信息
Mol Pharmacol. 2013 Mar;83(3):563-76. doi: 10.1124/mol.112.080697. Epub 2012 Nov 13.
Abstract
The epigenomic era has revealed a well-connected network of molecular processes that shape the chromatin landscape. These processes comprise abnormal methylomes, transcriptosomes, genome-wide histone post-transcriptional modifications patterns, histone variants, and noncoding RNAs. The mapping of these processes in large scale by chromatin immunoprecipitation sequencing and other methodologies in both cancer and normal cells reveals novel therapeutic opportunities for anticancer intervention. The goal of this minireview is to summarize pharmacological strategies to modify the epigenetic landscape of cancer cells. These approaches include the use of novel small molecule inhibitors of epigenetic processes specifically deregulated in cancer cells and the design of engineered proteins able to stably reprogram the epigenetic code in cancer cells in a way that is similar to normal cells.
摘要
表观基因组学时代揭示了一个分子过程的紧密连接网络，这些过程构成了异常的甲基组、转录组、全基因组组蛋白转录后修饰模式、组蛋白变体和非编码 RNA。通过染色质免疫沉淀测序和其他方法在癌症和正常细胞中大规模绘制这些过程，揭示了抗癌干预的新治疗机会。本篇综述的目的是总结修饰癌细胞表观基因组景观的药理学策略。这些方法包括使用专门在癌细胞中失调的表观遗传过程的新型小分子抑制剂，以及设计能够以类似于正常细胞的方式稳定重编程癌细胞中表观遗传密码的工程蛋白。
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