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

Stem Cell Reports. 2017 Jul 11;9(1):397-407. doi: 10.1016/j.stemcr.2017.05.026. Epub 2017 Jun 22.

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.

Keywords: DNA methylome; epigenome; human oocyte; in vitro maturation; non-CpG methylation; oocyte maturation; single cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • CpG Islands*
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Genome, Human
  • Humans
  • Oocytes / cytology*
  • Oocytes / metabolism
  • Oogenesis*
  • Single-Cell Analysis