title: Establishment of DNA methylation patterns of the Fibrillin1 (FBN1) gene in porcine embryos and tissues.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Arai
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Umeyama
authors.affiliation: Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Okazaki
authors.affiliation: Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hichiwa
authors.affiliation: Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yashima
authors.affiliation: Laboratory of Developmental Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakano
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Laboratory of Genomic Function Engineering, Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohgane
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro / Q000662:veterinary; D000071838:Fibrillin-1 / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013552:Swine
chemical_list: D000071838:Fibrillin-1
keywords: CpG island shore; DNA methylation; Fibrillin1 (FBN1); Hypo-allele