title: Allele-Specific Methylome and Transcriptome Analysis Reveals Widespread Imprinting in the Human Placenta.
abstract: DNA methylation is globally reprogrammed after fertilization, and as a result, the parental genomes have similar DNA-methylation profiles after implantation except at the germline differentially methylated regions (gDMRs). We and others have previously shown that human blastocysts might contain thousands of transient maternally methylated gDMRs (transient mDMRs), whose maternal methylation is lost in embryonic tissues after implantation. In this study, we performed genome-wide allelic DNA methylation analyses of purified trophoblast cells from human placentas and, surprisingly, found that more than one-quarter of the transient-in-embryo mDMRs maintained their maternally biased DNA methylation. RNA-sequencing-based allelic expression analyses revealed that some of the placenta-specific mDMRs were associated with expression of imprinted genes (e.g., TIGAR, SLC4A7, PROSER2-AS1, and KLHDC10), and three imprinted gene clusters were identified. This approach also identified some X-linked gDMRs. Comparisons of the data with those from other mammals revealed that genomic imprinting in the placenta is highly variable. These findings highlight the incomplete erasure of germline DNA methylation in the human placenta; understanding this erasure is important for understanding normal placental development and the pathogenesis of developmental disorders with imprinting effects.
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: okaehiro@m.tohoku.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okae
authors.affiliation: Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Toh
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Hatsune
authors.initials: H
authors.lastname: Chiba
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hiura
authors.affiliation: Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Shirane
authors.affiliation: Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.affiliation: Department of Obstetrics, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Gynecology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.affiliation: Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: tarima@med.tohoku.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arima
mesh_terms: D000483:Alleles; D051017:Apoptosis Regulatory Proteins; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D019175:DNA Methylation; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D050172:Genes, X-Linked; D015894:Genome, Human; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D010744:Phosphoric Monoester Hydrolases; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017423:Sequence Analysis, RNA; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C422022:SLC4A7 protein, human; D027982:Sodium-Bicarbonate Symporters; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human
keywords: DNA methylation; RNA sequencing; X-chromosome inactivation; genomic imprinting; germline differentially methylated region; human placenta; whole-genome bisulfite sequencing