Gopalakrishnan Suhasni, Van Emburgh Beth O, Robertson Keith D
Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Mutat Res. 2008 Dec 1;647(1-2):30-8. doi: 10.1016/j.mrfmmm.2008.08.006. Epub 2008 Aug 20.
DNA methylation is a heritable and stable epigenetic mark associated with transcriptional repression. Changes in the patterns and levels of global and regional DNA methylation regulate development and contribute directly to disease states such as cancer. Recent findings provide intriguing insights into the epigenetic crosstalk between DNA methylation, histone modifications, and small interfering RNAs in the control of cell development and carcinogenesis. In this review, we summarize the recent studies in DNA methylation primarily focusing on the interplay between different epigenetic modifications and their potential role in gene silencing in development and disease. Although the molecular mechanisms involved in the epigenetic crosstalk are not fully understood, unraveling their precise regulation is important not only for understanding the underpinnings of cellular development and cancer, but also for the design of clinically relevant and efficient therapeutics using stem cells and anticancer drugs that target tumor initiating cells.
DNA甲基化是一种与转录抑制相关的可遗传且稳定的表观遗传标记。整体和区域DNA甲基化模式及水平的变化调节发育,并直接导致诸如癌症等疾病状态。最近的研究结果为DNA甲基化、组蛋白修饰和小干扰RNA在细胞发育和致癌作用控制中的表观遗传相互作用提供了有趣的见解。在本综述中,我们总结了DNA甲基化的最新研究,主要关注不同表观遗传修饰之间的相互作用及其在发育和疾病中基因沉默的潜在作用。尽管表观遗传相互作用所涉及的分子机制尚未完全了解,但阐明其精确调控不仅对于理解细胞发育和癌症的基础很重要,而且对于设计使用干细胞和靶向肿瘤起始细胞的抗癌药物的临床相关且有效的疗法也很重要。