High Def DNA Methylome Maps Point Out Male and Female Germ Cell Differences

What sets males and females apart? Actually, let’s not head there, but how about at the methylome level? Quite a bit it appears. In a recent paper, researchers from Japan report that male and female primordial germ cells (PGCs) have different methylomes during development—at least in mice.

While these germ cells divide and move to the right place in early development, PGCs get reprogrammed epigenetically—histones leave, histones jump on; histones get modified; and DNA gets demethylated and then some of it gets methylated again.

But the researchers explain that detailed DNA methylation studies on PGCs have had their problems. Some methods require lots of DNA, but PGCs samples are small that these methods don’t really work well. Other studies suffer from low coverage or are limited to CpG-rich sequences.

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That’s why these researchers used whole-genome shotgun bisulfite sequencing. This method gives quantitative info about DNA methylation at single-base resolution. They also made a whole new library in order to analyze tiny, nanogram amounts of sample. Here’s some of what they learned with their high-res methylome maps:

  • They found sex- and chromosome-specific differences in the PGC methylomes during development.
  • Male and female PGCs differed in methylation at “preferentially methylated regions” before and after sex determination.
  • Male, but not female, PGCs had lots of non-CpG methylation during a later developmental stage.
  • Transposable elements were resistant to “global” demethylation during sex determination.

“Our data establish the basis for future studies on the role of epigenetic modifications in germline development and other biological processes,” shared Dr. Tomohiro Kono, a talented researcher involved with the work.

Read more at Genome Research, February 2013.