title: Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.
abstract: Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.
authors.affiliation: Department of Medical Microbiology and Immunology, The University of California Davis School of Medicine, Davis, California, United States of America; University of California Davis Genome Center, University of California Davis, Davis, California, United States of America; University of California Davis MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Diane I
authors.initials: DI
authors.lastname: Schroeder
authors.affiliation: Department of Population Health and Reproduction, UC Davis School of Veterinary Medicine, Davis, California, United States of America.
authors.forename: Kartika
authors.initials: K
authors.lastname: Jayashankar
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Kory C
authors.initials: KC
authors.lastname: Douglas
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, California, United States of America.
authors.forename: Twanda L
authors.initials: TL
authors.lastname: Thirkill
authors.affiliation: Department of Surgical and Radiological Sciences, University of California School of Veterinary Medicine, Davis, California, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: York
authors.affiliation: Department of Surgical and Radiological Sciences, University of California School of Veterinary Medicine, Davis, California, United States of America.
authors.forename: Pete J
authors.initials: PJ
authors.lastname: Dickinson
authors.affiliation: Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Bastrop, Texas, United States of America.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Williams
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Samollow
authors.affiliation: Department of Animal Science, University of California Davis, Davis, California, United States of America.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Ross
authors.affiliation: Department of Population Health and Reproduction, UC Davis School of Veterinary Medicine, Davis, California, United States of America.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Bannasch
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, California, United States of America.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Douglas
authors.affiliation: Department of Medical Microbiology and Immunology, The University of California Davis School of Medicine, Davis, California, United States of America; University of California Davis Genome Center, University of California Davis, Davis, California, United States of America; University of California Davis MIND Institute, University of California Davis, Sacramento, California, United States of America.
authors.forename: Janine M
authors.initials: JM
authors.lastname: LaSalle
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019175:DNA Methylation; D004285:Dogs; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005260:Female; D006736:Horses; D008253:Macaca mulatta; D051379:Mice; D009865:Oocytes / Q000502:physiology; D016366:Open Reading Frames; D009893:Opossums; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D012453:Saimiri; D013045:Species Specificity; D014158:Transcription, Genetic