DNA甲基转移酶在表观遗传学中的应用研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2024-0526

摘要/Abstract

摘要：

DNA甲基转移酶是一类在DNA甲基化过程中起到关键作用的酶。在生物体内，DNA甲基转移酶可以将甲基基团添加到核酸分子上，从而引入DNA甲基化修饰，改变遗传表现并调控基因表达。DNA甲基转移酶可以在体外进行融合重组表达，并导入细胞在染色质上引入人为的DNA甲基化修饰。利用这一特性，近年来，科研人员通过对基因组特定位置进行甲基化标记，并结合高通量测序，开发了多种基于DNA甲基转移酶的表观遗传测序技术，其应用包括染色质可及性测量、核小体定位、转录因子印迹和组蛋白修饰检测等。这些技术在获得表观遗传修饰信息的同时也可以获得基因组学信息以及内源性的DNA甲基化信息，因此成为了表观遗传学的重要检测方法。本文介绍了表观遗传修饰研究方法，综述了多种基于DNA甲基转移酶检测表观遗传修饰的测序技术的原理及应用，并对其未来的发展进行了讨论与展望，以期为表观遗传学的研究提供参考。

关键词: DNA甲基转移酶, DNA甲基化, 染色质可及性, DNA-蛋白质互作, 测序技术

Abstract:

DNA methyltransferases are a class of enzymes that play a key role in the process of DNA methylation. In living organisms, DNA methyltransferases add methyl groups to nucleic acid molecules, introduce DNA methylation modifications, alter epigenetic modifications, and regulate gene expression. DNA methyltransferases can be in fusion recombination expression in vitro and introduce into cells to have artificial DNA methylation modifications on chromatin. Taking advantage of this feature, in recent years, researchers have developed a variety of epigenetic sequencing technologies based on DNA methyltransferases by methylation labeling of specific locations in the genome, combined with high-throughput sequencing. These applications include chromatin accessibility measurement, nucleosome localization, transcription factor footprints, and histone modification assays. These techniques can obtain not only epigenetic information, but also genomic information and endogenous DNA methylation information, thus they have gradually become the important methods of epigenetics. In this paper, we briefly introduce the previous research methods, review the principles and applications of a variety of recent technologies based on DNA methyltransferase for the detection of epigenetic modifications, and discuss and prospect their future development, aiming to provide a reference for epigenetic research.

Key words: DNA methyltransferase, DNA methylation, chromatin accessibility, DNA-protein interaction, sequencing technology

周文健, 崔晓楠, 施威扬. DNA甲基转移酶在表观遗传学中的应用研究进展[J]. 生物技术通报, 2025, 41(2): 30-39.

ZHOU Wen-jian, CUI Xiao-nan, SHI Wei-yang. Research Progress in the Application of DNA Methyltransferases in Epigenetics[J]. Biotechnology Bulletin, 2025, 41(2): 30-39.

图/表 4

表1 三种技术的应用及方法学比较

Table 1 Comparison of applications and methodologies of three technologies

技术

Technology

应用

Application

酶使用类型

Type of enzyme

引入甲基化

Introducing methylation type

抗体使用

Application of antibody

反应方式

Mode of reaction

测序方法 Sequencing method

M.CviPI/M.SssI/EcoGII

图1 NOMe-seq技术和nanoNOMe-seq技术原理A：核小体定位及DNA甲基化组测序（NOMe-seq）；B：核小体定位及DNA甲基化组纳米孔测序（nanoNOMe-seq）

Fig. 1 Principle of NOMe-seq and nanoNOMe-seq technologyA: Nucleosome occupancy and methylome sequencing (NOMe-seq ). B: Nanopore sequencing of nucleosome occupancy and methylome (nanoNOMe-seq)

图2 SMAC-seq技术原理

Fig. 2 Principle of SMAC-seq technology

图3 DiMeLo-seq技术原理

Fig. 3 Principle of DiMeLo-seq technology

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