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

doi:10.1093/molbev/msx297

Landscape of DNA Methylation on the Marsupial X

Mol Biol Evol. 2018 Feb 1;35(2):431-439. doi: 10.1093/molbev/msx297.

Authors

Shafagh A Waters¹, Alexandra M Livernois², Hardip Patel³, Denis O'Meally⁴, Jeff M Craig^{5

6}, Jennifer A Marshall Graves⁷, Catherine M Suter^{8

9}, Paul D Waters¹

Affiliations

¹ School of Biotechnology & Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW, Australia.
² Institute for Applied Ecology, University of Canberra, Canberra, ACT, Australia.
³ John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
⁴ Center for Gene Therapy, Beckman Research Institute of the City of Hope, Duarte, CA.
⁵ Early Life Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.
⁶ Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia.
⁷ School of Life Science, La Trobe University, Melbourne, VIC, Australia.
⁸ Division of Molecular Structural and Computational Biology, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
⁹ Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

PMID: 29161408
DOI: 10.1093/molbev/msx297

Abstract

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.

Keywords: X chromosome inactivation; differential methylation; evolution; genomics; mammal; sex chromosomes.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chickens
DNA Methylation*
Female
Male
Marsupialia / genetics*
Mice
Sex Chromosomes*
Transcription Initiation Site*
X Chromosome Inactivation*