Establishment of DNA methylation patterns of the <i>Fibrillin1</i> (<i>FBN1</i>) gene in porcine embryos and tissues

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  • ARAI Yoshikazu
    Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Laboratory of Veterinary Biochemistry and Molecular Biology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan
  • UMEYAMA Kazuhiro
    Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Meiji University International Institute for Bio-Resource Research (MUIIBR), Kanagawa 214-8571, Japan
  • TAKEUCHI Kenta
    Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • OKAZAKI Natsumi
    Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • HICHIWA Naomi
    Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • YASHIMA Sayaka
    Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • NAKANO Kazuaki
    Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan
  • NAGASHIMA Hiroshi
    Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan Meiji University International Institute for Bio-Resource Research (MUIIBR), Kanagawa 214-8571, Japan
  • OHGANE Jun
    Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan

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  • Establishment of DNA methylation patterns of the Fibrillin1 (FBN1) gene in porcine embryos and tissues

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<p> DNA methylation in transcriptional regulatory regions is crucial for gene expression. The DNA methylation status of the edges of CpG islands, called CpG island shore, is involved in tissue/cell-type-specific gene expression. Haploinsufficiency diseases are caused by inheritance of one mutated null allele and are classified as autosomal dominant. However, in the same pedigree, phenotypic variances are observed despite the inheritance of the identical mutated null allele, including Fibrillin1 (FBN1), which is responsible for development of the haploinsufficient Marfan disease. In this study, we examined the relationship between gene expression and DNA methylation patterns of the FBN1 CpG island shore focusing on transcriptionally active hypomethylated alleles (Hypo-alleles). No difference in the DNA methylation level of FBN1 CpG island shore was observed in porcine fetal fibroblast (PFF) and the liver, whereas FBN1 expression was higher in PFF than in the liver. However, Hypo-allele ratio of the FBN1 CpG island shore in PFF was higher than that in the liver, indicating that Hypo-allele ratio of the FBN1 CpG island shore likely correlated with FBN1 expression level. In addition, oocyte-derived DNA hypermethylation in preimplantation embryos was erased until the blastocyst stage, and re-methylation of the FBN1 CpG island shore was observed with prolonged in vitro culture of blastocysts. These results suggest that the establishment of the DNA methylation pattern within the FBN1 CpG island shore occurs after the blastocyst stage, likely during organogenesis. In conclusion, Hypo-allele ratios of the FBN1 CpG island shore correlated with FBN1 expression levels in porcine tissues.</p>

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