<br>DNA 甲基化调节功能和组蛋白赖氨酸甲基化串扰的机制,Journal of Molecular Biology

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DNA 甲基化调节功能和组蛋白赖氨酸甲基化串扰的机制
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2023-12-12 , DOI: 10.1016/j.jmb.2023.168394
Bailey M Tibben ₁ , Scott B Rothbart ₁

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DNA 甲基化是一种经过充分研究的表观遗传修饰，在调节基因表达、维持基因组完整性和决定细胞命运方面具有关键作用。在关键发育阶段，特定细胞类型中 DNA 甲基化模式是如何建立和维持的，目前仍在阐明。然而，过去二十年的研究有助于我们理解其他表观遗传过程对 DNA 甲基化的调控。具体而言，组蛋白关键残基上的赖氨酸甲基化已被证明有助于 DNA 甲基转移酶（DNMT）活性的变构调节。在这篇综述中，我们通过综合该领域的最新关键研究，讨论了 DNA 甲基化和组蛋白赖氨酸甲基化作为基因组功能的表观遗传调节因子之间的动态相互作用。以 DNMT3 酶为重点，我们讨论了 DNA 甲基化和组蛋白赖氨酸甲基化串扰在基因表达调节和基因组完整性维持中的机制。此外，我们讨论了组蛋白赖氨酸甲基化和 DNA 甲基化各个位点平衡的改变如何导致人类发育障碍和癌症。最后，我们提供了对该领域当前方向的看法，并强调了需要继续研究和开发的领域。

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Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation

DNA methylation is a well-studied epigenetic modification that has key roles in regulating gene expression, maintaining genome integrity, and determining cell fate. Precisely how DNA methylation patterns are established and maintained in specific cell types at key developmental stages is still being elucidated. However, research over the last two decades has contributed to our understanding of DNA methylation regulation by other epigenetic processes. Specifically, lysine methylation on key residues of histone proteins has been shown to contribute to the allosteric regulation of DNA methyltransferase (DNMT) activities. In this review, we discuss the dynamic interplay between DNA methylation and histone lysine methylation as epigenetic regulators of genome function by synthesizing key recent studies in the field. With a focus on DNMT3 enzymes, we discuss mechanisms of DNA methylation and histone lysine methylation crosstalk in the regulation of gene expression and the maintenance of genome integrity. Further, we discuss how alterations to the balance of various sites of histone lysine methylation and DNA methylation contribute to human developmental disorders and cancers. Finally, we provide perspectives on the current direction of the field and highlight areas for continued research and development.

更新日期：2023-12-12

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