Comparison of global DNA methylation analysis by whole genome bisulfite sequencing and the Infinium Mouse Methylation BeadChip using fresh and fresh-frozen mouse epidermis

Epigenetics. 2023 Dec;18(1):2144574. doi: 10.1080/15592294.2022.2144574. Epub 2022 Nov 14.

Abstract

Until recently, studying the murine methylome was restricted to sequencing-based methods. In this study we compared the global DNA methylation levels of hairless mouse epidermis using the recently released Infinium Mouse Methylation BeadChip from Illumina and whole genome bisulphite sequencing (WGBS). We also studied the effect of sample storage conditions by using fresh and fresh-frozen epidermis. The DNA methylation levels of 123,851 CpG sites covered by both the BeadChip and WGBS were compared. DNA methylation levels obtained with WGBS and the BeadChip were strongly correlated (Pearson correlation r = 0.984). We applied a threshold of 15 reads for the WGBS methylation analysis. Even at a threshold of 10 reads, we observed no substantial difference in DNA methylation levels compared with that obtained with the BeadChip. The DNA methylation levels from the fresh and the fresh-frozen samples were strongly correlated when analysed with both the BeadChip (r = 0.999) and WGBS (r = 0.994). We conclude that the two methods of analysis generally work equally well for studies of DNA methylation of mouse epidermis and find that fresh and fresh-frozen epidermis can generally be used equally well. The choice of method will depend on the specific study's aims and the available resources in the laboratory.

Keywords: CpG methylation; DNA methylation; Infinium Mouse Methylation BeadChip; Whole genome bisulphite sequencing; epidermis; hairless mice.

MeSH terms

  • Animals
  • CpG Islands
  • DNA Methylation*
  • Genome, Human*
  • Humans
  • Mice
  • Sequence Analysis, DNA / methods
  • Sulfites
  • Whole Genome Sequencing / methods

Substances

  • hydrogen sulfite
  • Sulfites

Grants and funding

The work was funded by Copenhagen University Hospital, Bispebjerg and Frederiksberg and the Lundbeck Foundation (R307-2018- 3318).