DNA methyltransferase (Dnmt) silencing causes increased Cdx2 and Nanog levels in surviving embryos.

IF 1 4区 生物学 Q4 DEVELOPMENTAL BIOLOGY
Fatma Uysal, Gozde Sukur, Nazlican Bozdemir, Ozgur Cinar
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引用次数: 1

Abstract

Epigenetic mechanisms are one of the essential regulators of gene expression which do not involve altering the primary nucleotide sequence. DNA methylation is considered among the most prominent epigenetic mechanisms in controlling the functions of genes related to cell differentiation, cell cycle, cell survival, autophagy, and embryo development. DNA methyl transferases (Dnmts) control DNA methylation, the levels of which are differentially altered during embryonic development, and may determine cell differentiation fate as in the case of pluripotent inner cell mass (ICM) or trophectoderm (TE). In this study, we aimed to analyze the role of Dnmt1 and Dnmt3a enzymes in ICM (using the Nanog marker) and TE (using the Cdx2 marker) differentiation, autophagy (using p62 marker), reactive oxygen species (ROS) production, and apoptosis (using TUNEL) during mouse preimplantation embryo development. Following knockdown of Dnmt1 and Dnmt3a in zygotes, expression levels of Cdx2 in the trophectoderm and Nanog in the inner cell mass were measured, as well as p62 levels, reactive oxygen species (ROS) production, and apoptosis levels after 96 hours in embryo culture. We found that knockdown of Dnmt1 or Dnmt3a significantly induced Cdx2 and Nanog expression. Similarly, p62 expression, ROS levels and apoptosis significantly increased after silencing. This study shows that Dnmt genes are highly crucial for embryonic fate determination and survival. Further studies are required to reveal the specific targets of these methylation processes related to cell differentiation, survival, autophagy, and ROS production in mouse and human preimplantation embryos.

DNA甲基转移酶(Dnmt)沉默导致存活胚胎中Cdx2和Nanog水平升高。
表观遗传机制是基因表达的重要调控机制之一,它不涉及改变初级核苷酸序列。DNA甲基化被认为是控制与细胞分化、细胞周期、细胞存活、自噬和胚胎发育相关的基因功能的最重要的表观遗传机制之一。DNA甲基转移酶(Dnmts)控制DNA甲基化,其水平在胚胎发育过程中发生差异改变,并可能决定细胞分化命运,如多能性内细胞团(ICM)或滋养外胚层(TE)。在本研究中,我们旨在分析Dnmt1和Dnmt3a酶在小鼠植入前胚胎发育过程中ICM(使用Nanog标记)和TE(使用Cdx2标记)分化、自噬(使用p62标记)、活性氧(ROS)产生和凋亡(使用TUNEL)中的作用。在受精卵中敲除Dnmt1和Dnmt3a后,测定滋养外胚层Cdx2和内细胞团中Nanog的表达水平,以及胚胎培养96 h后p62水平、活性氧(ROS)产生和凋亡水平。我们发现敲低Dnmt1或Dnmt3a可显著诱导Cdx2和Nanog的表达。同样,沉默后p62表达、ROS水平和细胞凋亡显著增加。该研究表明,Dnmt基因对胚胎命运的决定和存活至关重要。需要进一步的研究来揭示这些甲基化过程与小鼠和人类植入前胚胎中细胞分化、存活、自噬和ROS产生相关的具体靶点。
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来源期刊
CiteScore
1.90
自引率
0.00%
发文量
16
审稿时长
2 months
期刊介绍: The International Journal of Developmental Biology (ISSN: 0214- 6282) is an independent, not for profit scholarly journal, published by scientists, for scientists. The journal publishes papers which throw light on our understanding of animal and plant developmental mechanisms in health and disease and, in particular, research which elucidates the developmental principles underlying stem cell properties and cancer. Technical, historical or theoretical approaches also fall within the scope of the journal. Criteria for acceptance include scientific excellence, novelty and quality of presentation of data and illustrations. Advantages of publishing in the journal include: rapid publication; free unlimited color reproduction; no page charges; free publication of online supplementary material; free publication of audio files (MP3 type); one-to-one personalized attention at all stages during the editorial process. An easy online submission facility and an open online access option, by means of which papers can be published without any access restrictions. In keeping with its mission, the journal offers free online subscriptions to academic institutions in developing countries.
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