Abnormal DNA methylation of the Oct-4 enhancer region in cloned mouse embryos
Miyuri Kawasumi
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Department of Anatomy and Reproductive Biology, Institute for Biogenesis Research, School of Medicine, University of Hawaii, Honolulu, Hawaii
Search for more papers by this authorYuichi Unno
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorToshiki Matsuoka
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorMegumi Nishiwaki
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorMasayuki Anzai
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorTomoko Amano
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorTasuku Mitani
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorHiromi Kato
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorKazuhiro Saeki
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorYoshihiko Hosoi
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorAkira Iritani
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorSatoshi Kishigami
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorCorresponding Author
Kazuya Matsumoto
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan.Search for more papers by this authorMiyuri Kawasumi
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Department of Anatomy and Reproductive Biology, Institute for Biogenesis Research, School of Medicine, University of Hawaii, Honolulu, Hawaii
Search for more papers by this authorYuichi Unno
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorToshiki Matsuoka
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorMegumi Nishiwaki
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorMasayuki Anzai
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorTomoko Amano
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorTasuku Mitani
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorHiromi Kato
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorKazuhiro Saeki
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorYoshihiko Hosoi
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorAkira Iritani
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorSatoshi Kishigami
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Search for more papers by this authorCorresponding Author
Kazuya Matsumoto
Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan
Institute of Advanced Technology, Kinki University, Wakayama, Japan
930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan.Search for more papers by this authorAbstract
Oct-4 is essential for normal embryonic development, and abnormal Oct-4 expression in cloned embryos contributes to cloning inefficiency. However, the causes of abnormal Oct-4 expression in cloned embryos are not well understood. As DNA methylation in regulatory regions is known to control transcriptional activity, we investigated the methylation status of three transcriptional regulatory regions of the Oct-4 gene in cloned mouse embryos—the distal enhancer (DE), the proximal enhancer (PE), and the promoter regions. We also investigated the level of Oct-4 gene expression in cloned embryos. Immunochemistry revealed that 85% of cloned blastocysts expressed Oct-4 in both trophectoderm and inner cell mass cells. DNA methylation analysis revealed that the PE region methylation was greater in cloned morulae than in normal morulae. However, the same region was less methylated in cloned blastocysts than in normal blastocysts. We found abnormal expression of de novo methyltransferase 3b in cloned blastocysts. These results indicate that cloned embryos have aberrant DNA methylation in the CpG sites of the PE region of Oct-4, and this may contribute directly to abnormal expression of this gene in cloned embryos. Mol. Reprod. Dev. 76: 342–350, 2009. © 2008 Wiley-Liss, Inc.
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