title: The HUS1B promoter is hypomethylated in the placentas of low-birth-weight infants.
abstract: Aberrant DNA methylation is associated with a range of human disorders. To identify differences in DNA methylation of gene promoters between placentas of low-birth-weight (LBW) and normal-birth-weight (NBW) infants, we screened 8091 genes for aberrant methylation in placentas using microarray-based integrated analysis of methylation by isoschizomers (MIAMI). Seven candidate genes for hypomethylation in the placentas of LBW infants were selected. Among these candidates, COBRA analyses suggested that the HUS1B gene was hypomethylated in some of the placentas. Quantitative methylation analyses by bisulfite-pyrosequencing indicated that the promoter region of the gene was hypomethylated in three of the 86 placentas analyzed. The HUS1B promoter was highly methylated in two cell lines derived from trophoblastic cells. Gene expression increased when the promoter was demethylated by 5Aza-dC treatment. This suggests that hypomethylation of HUS1B alters gene expression in the placenta and that this dysregulated gene expression may contribute to the pathogenesis of LBW by affecting placental functions involved in fetal growth.
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan; Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.
authors.forename: Janette Mareska
authors.initials: JM
authors.lastname: Rumbajan
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yatsuki
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishioka
authors.affiliation: Division of Pathology, Department of Pathology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Division of Pathology, Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.affiliation: Division of Pathology, Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Obstetrics and Gynecology, Saimata Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan. Electronic address: soejimah@cc.saga-u.ac.jp.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan. Electronic address: joh@cc.saga-u.ac.jp.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Joh
mesh_terms: D001724:Birth Weight; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D046888:Tissue Array Analysis
chemical_list: D018797:Cell Cycle Proteins; C462949:HUS1B protein, human
keywords: DNA methylation; HUS1B; LBW; Placenta; SGA