社论——DNA 甲基转移酶在表观基因组中的作用。

Editorial-Role of DNA Methyltransferases in the Epigenome.

机构信息

Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, 70569 Stuttgart, Germany.

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.

出版信息

Genes (Basel). 2019 Jul 30;10(8):574. doi: 10.3390/genes10080574.

DOI:10.3390/genes10080574

PMID:31366147

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6723798/

Abstract

DNA methylation, a modification found in most species, regulates chromatin functions in conjunction with other epigenome modifications, such as histone post-translational modifications and non-coding RNAs. In mammals, DNA methylation has essential roles in development by orchestrating the generation and maintenance of the phenotypic diversity of human cell types. This Special Issue of Genes contains eight review articles, which cover several aspects of epigenome regulation by DNA methyltransferases (DNMTs), the enzymes responsible for the introduction of DNA methylation. The manuscripts present the most recent advances regarding the structure and function of DNMTs, their targeting and regulation by interacting factors and chromatin modifications, and the roles of DNMTs in mammalian development and human diseases. However, many aspects of these important enzymes are still insufficiently understood. Potential directions of future work are the regulation of DNMTs by post-translational modifications and their connection to cellular signaling and second messenger cascades on one hand and to large multifactorial epigenetic chromatin circuits on the other. Additionally, technical advancements, including the availability of designer nucleosomes and the rapid development of cryo-electron microscopy are expected to trigger breakthrough discoveries in this exciting field.

摘要

DNA 甲基化是一种在大多数物种中发现的修饰方式，它与其他表观遗传修饰（如组蛋白翻译后修饰和非编码 RNA）一起调节染色质功能。在哺乳动物中，DNA 甲基化通过协调人类细胞类型的表型多样性的产生和维持，在发育中发挥着重要作用。本《基因》特刊包含 8 篇综述文章，涵盖了 DNA 甲基转移酶（DNMTs）对表观基因组调控的几个方面，DNMTs 是负责引入 DNA 甲基化的酶。这些手稿介绍了关于 DNMTs 的结构和功能、它们与相互作用因子和染色质修饰的靶向和调节、以及在哺乳动物发育和人类疾病中 DNMTs 的作用的最新进展。然而，这些重要酶的许多方面仍然了解不足。未来工作的潜在方向是一方面研究 DNA 甲基转移酶的翻译后修饰及其与细胞信号和第二信使级联的联系，另一方面研究它们与大型多因素表观遗传染色质回路的联系。此外，技术进步，包括设计的核小体的可用性和冷冻电子显微镜的快速发展，预计将在这个令人兴奋的领域引发突破性发现。