Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 9016, Dunedin, New Zealand.
Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 9016, Dunedin, New Zealand.
Trends Cancer. 2020 May;6(5):392-406. doi: 10.1016/j.trecan.2020.02.007. Epub 2020 Mar 4.
DNA methylation is a stable epigenetic modification that contributes to the spatiotemporal regulation of gene expression. The manner in which DNA methylation contributes to transcriptional control is dependent on the biological context, including physiological state and the properties of the DNA itself. Classically, dense promoter DNA methylation is associated with transcriptional repression. However, growing evidence suggests that this association may not always hold true, and promoter hypermethylation now also appears to be associated with high transcriptional activity. Furthermore, in a selection of contexts, increasing levels of promoter methylation correlate directly with increased gene expression. These findings postulate a context-dependent model whereby epigenetic contributions to transcriptional regulation occur in a more complex and dynamic manner. We present current evidence documenting promoter hypermethylation and high levels of gene expression, offer insights into the possible mechanisms by which this occurs, and discuss the potential implications for both research and clinical applications.
DNA 甲基化是一种稳定的表观遗传修饰，有助于基因表达的时空调节。DNA 甲基化如何促进转录调控取决于生物背景，包括生理状态和 DNA 本身的性质。经典上，密集的启动子 DNA 甲基化与转录抑制有关。然而，越来越多的证据表明，这种关联并不总是成立的，启动子超甲基化现在也与高转录活性有关。此外，在一些情况下，启动子甲基化水平的增加与基因表达的增加直接相关。这些发现提出了一种依赖于上下文的模型，其中表观遗传对转录调控的贡献以更复杂和动态的方式发生。我们提出了目前有文献记录的启动子超甲基化和高水平基因表达的证据，探讨了这种现象发生的可能机制，并讨论了其对研究和临床应用的潜在影响。
