Hsiao Shu-Huei, Huang Tim H-M, Leu Yu-Wei
Human Epigenomics Center, Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan.
Semin Cancer Biol. 2009 Jun;19(3):198-208. doi: 10.1016/j.semcancer.2009.02.015. Epub 2009 Mar 5.
Epigenetic events like DNA methylation are known to regulate gene expression, and dysregulation of these events is associated with neoplastic proliferation. Here, we provide a step-by-step review of the approach that has gradually developed to identify critical DNA methylation during neoplasia. DNA methylation has first been tightly linked to the regulation of gene expression and functions. Next, the clinical importance of such DNA methylation has been probed by inducing loss of the maintenance of normal DNA methylation, which has been found to trigger onset of disease. Methylation changes can be signal-specific and lineage-specific, providing a record what cells have encountered and what they have become. Comparison of methylation associated with normal cellular differentiation and abnormal cell fate changes is expected to uncover critical methylation changes. We also propose a specific scheme that can be used to excavate critical DNA methylation associated with cell evolution.
已知DNA甲基化等表观遗传事件可调节基因表达，而这些事件的失调与肿瘤增殖有关。在此，我们逐步回顾了在肿瘤形成过程中逐渐发展起来的用于识别关键DNA甲基化的方法。DNA甲基化首先与基因表达和功能的调控紧密相关。接下来，通过诱导正常DNA甲基化维持功能的丧失来探究这种DNA甲基化的临床重要性，发现这会引发疾病的发生。甲基化变化可以是信号特异性和谱系特异性的，记录了细胞所经历的以及它们所变成的状态。比较与正常细胞分化和异常细胞命运变化相关的甲基化有望揭示关键的甲基化变化。我们还提出了一种可用于挖掘与细胞进化相关的关键DNA甲基化的具体方案。
