Genome-wide, Single-Cell DNA Methylomics Reveals Increased Non-CpG Methylation during Human Oocyte Maturation

Bo Yu, Xiao Dong, Silvia Gravina, Önder Kartal, Timothy Schimmel, Jacques Cohen, Drew Tortoriello, Raifa Zody, R. David Hawkins, Jan Vijg

Research output: Contribution to journalArticlepeer-review

Abstract

The establishment of DNA methylation patterns in oocytes is a highly dynamic process marking gene-regulatory events during fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming in primordial germ cells, how and when DNA methylation is re-established in developing human oocytes remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing, we describe DNA methylation patterns in three different maturation stages of human oocytes. We found that while broad-scale patterns of CpG methylation have been largely established by the immature germinal vesicle stage, localized changes continue into later development. Non-CpG methylation, on the other hand, undergoes a large-scale, generalized remodeling through the final stage of maturation, with the net overall result being the accumulation of methylation as oocytes mature. The role of the genome-wide, non-CpG methylation remodeling in the final stage of oocyte maturation deserves further investigation.

Original languageEnglish (US)
Pages (from-to)397-407
Number of pages11
JournalStem Cell Reports
Volume9
Issue number1
DOIs
StatePublished - Jul 11 2017
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Adam Auton, PhD, for guidance in data analysis and statistics and Moonsook Lee for technical guidance in single-cell WGBS library preparation. This work was supported by grants from the Reproductive Scientist Development Program (NIH 5K12HD000849), American Society for Reproductive Medicine, Howard and Georgeanna Jones Foundation for Reproductive Medicine, Einstein Nathan Shock Center of Excellence in Basic Biology of Aging (to B.Y.); NIH P01AG017242, the Glenn Foundation, and the SENS Foundation (to J.V.).

Publisher Copyright:
© 2017 The Author(s)

Keywords

  • DNA methylome
  • epigenome
  • human oocyte
  • in vitro maturation
  • non-CpG methylation
  • oocyte maturation
  • single cell

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