Epigenetics: what happened with this?

In 2012, Yan Li & Chris O’Neill published a paper about DNA methylation in the early mouse embryo, claiming that the first wave of demethylation following fertilisation in the mouse embryo doesn’t happen.

This picture, figure 1 from Seisenberger & al (2013; license: cc:by 3.0), shows what it is about. The curves represent DNA methylation level, and first time the curves drop represents the demethylation in question:


Li & O’Neill used a variation of immunostaining for methylated cytosine. Figures 8 and 3 summarise the results: eight shows embryos stained for methylated cytosine with two different preparation methods. The main claim of the paper is that the added trypsin treatment in the preparation helps unmask DNA methylation. So maybe the cytosine methylations are not removed, but temporarily hidden by something else. Figure 3 shows a Western blot for methyl-binding domain protein 1. The claim here is that if MBD1 is expressed, DNA methylation is also there. The obvious alternative hypothesis is that their variation on the protocol creates some kind of artefact and that MBD1 expression doesn’t matter.


Figure 8, Li & O’Neill (cc:by 3.0).

The paper has been cited mostly by review papers, and I haven’t seen any further news on the subject. Does anyone know if anything more has happened?


Li Y, O’Neill C (2012) Persistence of Cytosine Methylation of DNA following Fertilisation in the Mouse. PLoS ONE 7(1) e30687. doi:10.1371/journal.pone.0030687

Seisenberger, S., Peat, J. R., Hore, T. A., Santos, F., Dean, W., & Reik, W. (2013). Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philosophical Transactions of the Royal Society B: Biological Sciences 368(1609), 20110330.