title: Placental Hypomethylation Is More Pronounced in Genomic Loci Devoid of Retroelements.
abstract: The human placenta is hypomethylated compared to somatic tissues. However, the degree and specificity of placental hypomethylation across the genome is unclear. We assessed genome-wide methylation of the human placenta and compared it to that of the neutrophil, a representative homogeneous somatic cell. We observed global hypomethylation in placenta (relative reduction of 22%) compared to neutrophils. Placental hypomethylation was pronounced in intergenic regions and gene bodies, while the unmethylated state of the promoter remained conserved in both tissues. For every class of repeat elements, the placenta showed lower methylation but the degree of hypomethylation differed substantially between these classes. However, some retroelements, especially the evolutionarily younger Alu elements, retained high levels of placental methylation. Surprisingly, nonretrotransposon-containing sequences showed a greater degree of placental hypomethylation than retrotransposons in every genomic element (intergenic, introns, and exons) except promoters. The differentially methylated fragments (DMFs) in placenta and neutrophils were enriched in gene-poor and CpG-poor regions. The placentally hypomethylated DMFs were enriched in genomic regions that are usually inactive, whereas hypermethylated DMFs were enriched in active regions. Hypomethylation of the human placenta is not specific to retroelements, indicating that the evolutionary advantages of placental hypomethylation go beyond those provided by expression of retrotransposons and retrogenes.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand Gravida: National Centre for Growth and Development, University of Auckland, 1142, New Zealand Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand aniruddha.chatterjee@otago.ac.nz ian.morison@otago.ac.nz.
authors.forename: Aniruddha
authors.identifier: 0000-0001-7276-2248
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand Gravida: National Centre for Growth and Development, University of Auckland, 1142, New Zealand.
authors.forename: Erin C
authors.identifier: 0000-0001-5308-1033
authors.initials: EC
authors.lastname: Macaulay
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand.
authors.forename: Euan J
authors.identifier: 0000-0002-9615-5896
authors.initials: EJ
authors.lastname: Rodger
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Stockwell
authors.affiliation: Department of Mathematics and Statistics, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Parry
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Hester E
authors.initials: HE
authors.lastname: Roberts
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand Gravida: National Centre for Growth and Development, University of Auckland, 1142, New Zealand.
authors.forename: Tania L
authors.initials: TL
authors.lastname: Slatter
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Noelyn A
authors.identifier: 0000-0002-2401-9764
authors.initials: NA
authors.lastname: Hung
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Celia J
authors.initials: CJ
authors.lastname: Devenish
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand Gravida: National Centre for Growth and Development, University of Auckland, 1142, New Zealand aniruddha.chatterjee@otago.ac.nz ian.morison@otago.ac.nz.
authors.forename: Ian M
authors.identifier: 0000-0003-3616-0025
authors.initials: IM
authors.lastname: Morison
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D021901:DNA, Intergenic; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D007438:Introns; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D018626:Retroelements
chemical_list: D021901:DNA, Intergenic; D018626:Retroelements
keywords: hypomethylation; neutrophil; placenta; reduced representation bisulfite sequencing; retroelement