Department of Animal and Dairy Sciences, Mississippi State University, MS, USA.
Reprod Biomed Online. 2010 Feb;20(2):243-55. doi: 10.1016/j.rbmo.2009.11.006. Epub 2009 Dec 11.
DNA methylation involves biochemical modification of DNA by addition of methyl groups onto CpG dinucleotides, and this epigenetic mechanism regulates gene expression in disease and development. Mammalian DNA methyltransferases, DNMT (DNMT1, DNMT3A and DNMT3B), together with the accessory protein DNMT3L establish specific DNA methylation patterns in the genome during gametogenesis, embryogenesis and somatic tissue development. The present study addresses the structural and functional conservation of the DNMT in humans, mice and cattle and the patterns of mRNA abundance of the different enzymes during embryogenesis to improve understanding of epigenetic regulation in early development. The findings showed a high degree of structural and functional conservation among the human, mouse, and bovine DNMT. The results also showed similar patterns of transcript abundance for all of the proteins at different stages of early embryo development. Remarkably, all of the DNMT with an important role in DNA methylation (DNMT1, DNMT3A, DNMT3B, and DNMT3L) show a greater degree of structural similarity between human and bovine than that between human and mouse. These results have important implications for the selection of an appropriate model for study of DNA methylation during early development in humans.
DNA 甲基化涉及通过向 CpG 二核苷酸添加甲基基团对 DNA 进行生化修饰，这种表观遗传机制调节疾病和发育过程中的基因表达。哺乳动物 DNA 甲基转移酶（DNMT1、DNMT3A 和 DNMT3B）与辅助蛋白 DNMT3L 一起，在配子发生、胚胎发生和体组织发育过程中在基因组中建立特定的 DNA 甲基化模式。本研究旨在探讨人类、小鼠和牛的 DNMT 的结构和功能保守性，以及不同酶在胚胎发生过程中的 mRNA 丰度模式，以提高对早期发育中表观遗传调控的理解。研究结果表明，人类、小鼠和牛的 DNMT 在结构和功能上具有高度的保守性。结果还表明，所有蛋白质在早期胚胎发育的不同阶段的转录丰度模式相似。值得注意的是，所有在 DNA 甲基化中起重要作用的 DNMT（DNMT1、DNMT3A、DNMT3B 和 DNMT3L）在人与牛之间的结构相似性都大于人与鼠之间的结构相似性。这些结果对于选择合适的模型来研究人类早期发育过程中的 DNA 甲基化具有重要意义。
