Landscape of DNA Methylation on the Marsupial X

Shafagh A. Waters, Alexandra M. Livernois, Hardip Patel, Denis O'Meally, Jeff M. Craig, Jennifer A. Marshall Graves, Catherine M. Suter, Paul D. Waters

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


DNA methylation plays a key role in maintaining transcriptional silence on the inactive X chromosome of eutherian mammals. Beyond eutherians, there are limited genome wide data on DNA methylation from other vertebrates. Previous studies of X borne genes in various marsupial models revealed no differential DNA methylation of promoters between the sexes, leading to the conclusion that CpG methylation plays no role in marsupial X-inactivation. Using reduced representation bisulfite sequencing, we generated male and female CpG methylation profiles in four representative vertebrates (mouse, gray short-tailed opossum, platypus, and chicken). A variety of DNA methylation patterns were observed. Platypus and chicken displayed no large-scale differential DNA methylation between the sexes on the autosomes or the sex chromosomes. As expected, a metagene analysis revealed hypermethylation at transcription start sites (TSS) of genes subject to X-inactivation in female mice. This contrasted with the opossum, in which metagene analysis did not detect differential DNA methylation between the sexes at TSSs of genes subject to X-inactivation. However, regions flanking TSSs of these genes were hypomethylated. Our data are the first to demonstrate that, for genes subject to X-inactivation in both eutherian and marsupial mammals, there is a consistent difference between DNA methylation levels at TSSs and immediate flanking regions, which we propose has a silencing effect in both groups.

Original languageEnglish
Pages (from-to)431-439
Number of pages9
JournalMolecular Biology and Evolution
Issue number2
Publication statusPublished - Feb 2018
Externally publishedYes


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