{"title":"DNA methyltransferase (Dnmt) silencing causes increased Cdx2 and Nanog levels in surviving embryos.","authors":"Fatma Uysal, Gozde Sukur, Nazlican Bozdemir, Ozgur Cinar","doi":"10.1387/ijdb.230040oc","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>Dnmt1</i> and <i>Dnmt3a</i> 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.</p>","PeriodicalId":50329,"journal":{"name":"International Journal of Developmental Biology","volume":"67 1","pages":"1-8"},"PeriodicalIF":1.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Developmental Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1387/ijdb.230040oc","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
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.
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.