Shukla Vivek, Vaissière Thomas, Herceg Zdenko
International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
Mutat Res. 2008 Jan 1;637(1-2):1-15. doi: 10.1016/j.mrfmmm.2007.07.012. Epub 2007 Aug 1.
Cancers are traditionally viewed as a primarily genetic disorder, however this view has recently been modified by compelling evidence arguing that epigenetic events play important roles in most human cancers. Deregulation of epigenetic information (encoded in DNA methylation and histone modification patterns) in cells with pluripotent potential may alter defining properties of stem cells, self-renewal and differentiation potential, leading to cancer initiation and progression. The level of compaction of chromatin dictates accessibility to genomic DNA and therefore has a key role in establishing and maintaining distinct gene expression patterns and consequently pluripotent state and differentiation fates of stem cells. Unique properties of stem cells defined as "stemness" may be determined by acetylation and methylation of histones near gene promoters that regulate gene transcription, however these histone modifications elsewhere in the genome may also be important. In this review, we discuss new insights into possible mechanisms by which histone acetyltransferases (HATs) and histone acetylation in concert with other chromatin modifications may regulate pluripotency, and speculate how deregulation of histone marking may lead to tumourigenesis.
癌症传统上被视为一种主要的基因紊乱疾病，然而最近这一观点已被有力证据修正，这些证据表明表观遗传事件在大多数人类癌症中发挥着重要作用。具有多能潜能的细胞中表观遗传信息（由DNA甲基化和组蛋白修饰模式编码）的失调可能会改变干细胞的定义特性、自我更新和分化潜能，从而导致癌症的发生和发展。染色质的压缩程度决定了对基因组DNA的可及性，因此在建立和维持不同的基因表达模式以及干细胞的多能状态和分化命运方面起着关键作用。被定义为“干性”的干细胞的独特特性可能由调控基因转录的基因启动子附近组蛋白的乙酰化和甲基化决定，然而基因组中其他位置的这些组蛋白修饰可能也很重要。在这篇综述中，我们讨论了关于组蛋白乙酰转移酶（HATs）和组蛋白乙酰化与其他染色质修饰协同作用可能调控多能性的潜在机制的新见解，并推测组蛋白标记失调如何导致肿瘤发生。
