DNA methylation plays an important role during early embryo development. The longstanding paradigm of global loss of 5´-methylcytosine (5meC) over the first few cell-cycle of early development, catalysed via Tet-mediated conversion to 5´-hydroxymethylcytosine (5hmC) and subsequent base excision, has recently been challenged (1,2). Here we show that global levels of both 5meC and 5hmC persist throughout zygotic maturation and the first cell-cycles (to the 8-cell stage). By the morula stage, cells encased in an inner position show a ~ 50% reduction in global levels of 5meC and 5hmC and a further loss occurs in the inner cell mass (ICM) of the blastocyst stage embryo. High levels of both modifications persist in the outer cells of the morula and the resulting trophectoderm of the blastocyst stage embryo. The demethylated stage of the ICM is carried over into both the epiblast (UTF1-positive) and hypoblast (GATA6-positive) lineages, while the relatively high levels of the 5meC and 5hmC persist with differentiation of the TE into trophoblast (CDX2-positive) and trophoblast giant cells (Eomes-positive). This study redefines the dynamics of epigenetic programming in early development and shows that the global changes in the pattern of nuclear 5meC and 5hmC are early markers of commitment to the pluripotent lineage in the early embryo.

1. Li Y & O’Neill C (2012) PLoS One. 7(1): e30687

2. Li Y & O’Neill C (2013) PLoS One.8(5): e63689