DNA methylation in mammalian placentas

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 methylation 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. However, not all species have clear PMD/HMDs in their placentas. Instead what is conserved is higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification compared with the rest of the genome. As in human placenta, high gene body methylation is associated with higher gene expression across species. Analysis of DNA methylation in mouse and cow oocytes shows the same pattern of gene body methylation over many of the same genes as in the placenta, suggesting that this conserved pattern of active gene body methylation of the placenta may be established very early in development. MethylC-seq on placentas of 7 mammals, trophoblasts of rhesus, brains of 3 mammals, oocytes of cow, and human cordblood