title: Dynamics of TET family expression in porcine preimplantation embryos is related to zygotic genome activation and required for the maintenance of NANOG.
abstract: Dynamic changes in DNA methylation are observed during embryo development. Recent studies show that the TET family is involved in these changes by converting 5-methylcytosine (5mec) to 5-hydroxymethylcytosine (5hmec). Specifically, TET3 is responsible for the conversion in the early stages, and then TET1 is a key regulator at later stages of embryo development. From previous mouse reports and our preliminary data in porcine embryos, we hypothesized that TET1 becomes the main regulator at the time of the maternal to zygotic transition (MZT). Transcript abundance of TET3 was high only at the zygote and 2-cell stage. The abundance of TET1 mRNA was high in the blastocysts and TET1 protein was present at the 4-cell stage and the blastocysts. The dynamic was similar in porcine somatic cell nuclear transfer (SCNT) embryos however; abnormally upregulated TET3 was detected at the 4-cell stage. When transcription or translation was blocked at the 2-cell stage, TET3 mRNA remained high at the 4-cell stage suggesting that degradation of TET3 is related to the MZT. Downregulation of TET3 before fertilization resulted in the reduction of 5hmec in zygotes indicating that TET3 is a key molecule for 5hmec synthesis. This misregulation of 5hmec in zygotes also affected the level of NANOG expression in the blastocysts. We show here that the porcine TET family shows dynamic expression patterns during embryogenesis, and is responsible for the appearance of 5hmec in the zygotes by TET3. This appearance of 5hmec in zygote is important for the expression of NANOG in the blastocysts.
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA. Electronic address: leekil@missouri.edu.
authors: Kiho
authors: K
authors: Lee
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA.
authors: Jennifer
authors: J
authors: Hamm
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA.
authors: Kristin
authors: K
authors: Whitworth
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA.
authors: Lee
authors: L
authors: Spate
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA; Department of Animal Science and Technology, Sunchon National University, Suncheon, Jeonnam 540-742, South Korea.
authors: Kwang-Wook
authors: KW
authors: Park
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA.
authors: Clifton N
authors: CN
authors: Murphy
authors: Division of Animal Sciences, Animal Science Research Center, University of Missouri, Columbia, MO 65201, USA; National Swine Resource and Research Center, University of Missouri, Columbia, MO 65201, USA.
authors: Randall S
authors: RS
authors: Prather
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases / Q000235:genetics; D005306:Fertilization; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D006899:Mixed Function Oxygenases; D005810:Multigene Family; D000071317:Nanog Homeobox Protein; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D015053:Zygote / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C578792:TET3 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; 5hmec; 5mec; DNA methylation; DNA methyltransferases; DNMT; ICM; IVF; In vitro fertilization; MZT; Maternal to zygotic transition; Porcine embryos; SCNT; TE; TET; Ten-eleven translocation family; ZGA; inner cell mass; maternal to zygotic transition; somatic cell nuclear transfer; ten-eleven translocation; trophectoderm; zygotic genome activation