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DNMT1、DNMT3A 和 DNMT3B 蛋白在小鼠卵母细胞和早期胚胎中的表达不同。

DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos.

机构信息

Department of Histology and Embryology, Akdeniz University School of Medicine, Campus, 07070, Antalya, Turkey.

出版信息

J Mol Histol. 2017 Dec;48(5-6):417-426. doi: 10.1007/s10735-017-9739-y. Epub 2017 Oct 13.

Abstract

DNA methylation is one of the epigenetic mechanisms and plays important roles during oogenesis and early embryo development in mammals. DNA methylation is basically known as adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. This mechanism is composed of two main processes: de novo methylation and maintenance methylation, both of which are catalyzed by specific DNA methyltransferase (DNMT) enzymes. To date, six different DNMTs have been characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and DNMT3L. While DNMT1 primarily functions in maintenance methylation, both DNMT3A and DNMT3B are essentially responsible for de novo methylation. As is known, either maintenance or de novo methylation processes appears during oocyte and early embryo development terms. The aim of the present study is to investigate spatial and temporal expression levels and subcellular localizations of the DNMT1, DNMT3A, and DNMT3B proteins in the mouse germinal vesicle (GV) and metaphase II (MII) oocytes, and early embryos from 1-cell to blastocyst stages. We found that there are remarkable differences in the expressional levels and subcellular localizations of the DNMT1, DNMT3A and DNMT3B proteins in the GV and MII oocytes, and 1-cell, 2-cell, 4-cell, 8-cell, morula, and blastocyst stage embryos. The fluctuations in the expression of DNMT proteins in the analyzed oocytes and early embryos are largely compatible with DNA methylation changes and genomic imprintestablishment appearing during oogenesis and early embryo development. To understand precisemolecular biological meaning of differently expressing DNMTs in the early developmental periods, further studies are required.

摘要

DNA 甲基化是表观遗传机制之一,在哺乳动物的卵子发生和早期胚胎发育中发挥重要作用。DNA 甲基化通常是指在胞嘧啶-磷酸-鸟嘌呤(CpG)和非 CpG 二核苷酸位点中,胞嘧啶残基的第五个碳原子上添加一个甲基基团。该机制由两个主要过程组成:从头甲基化和维持甲基化,这两个过程均由特定的 DNA 甲基转移酶(DNMT)酶催化。迄今为止,已在哺乳动物中鉴定出六种不同的 DNMT,分别定义为 DNMT1、DNMT2、DNMT3A、DNMT3B、DNMT3C 和 DNMT3L。DNMT1 主要在维持甲基化中发挥作用,而 DNMT3A 和 DNMT3B 则主要负责从头甲基化。如前所述,无论是维持甲基化还是从头甲基化过程,在卵母细胞和早期胚胎发育过程中都有出现。本研究旨在探讨 DNMT1、DNMT3A 和 DNMT3B 蛋白在小鼠生发泡(GV)和中期 II(MII)卵母细胞以及从 1 细胞到囊胚阶段的早期胚胎中的空间和时间表达水平及亚细胞定位。结果发现,DNMT1、DNMT3A 和 DNMT3B 蛋白在 GV 和 MII 卵母细胞以及 1 细胞、2 细胞、4 细胞、8 细胞、桑椹胚和囊胚阶段胚胎中的表达水平和亚细胞定位存在显著差异。在分析的卵母细胞和早期胚胎中,DNMT 蛋白的表达波动与卵子发生和早期胚胎发育过程中出现的 DNA 甲基化变化和基因组印迹建立基本一致。为了理解早期发育阶段不同表达的 DNMT 分子生物学意义,还需要进一步研究。

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