The classical way of thinking about the development of the early mouse embryo has been that it is an essential prerequisite for cells to adopt differential, inside or outside positions for them to acquire differential expression of cell fate determining genes. However, over recent years it has been realised that important differences arise between cells in gene expression, cell fate and potential earlier than previously realised, before cells acquire specific positions. We have found that levels of methylation of histone H3 at specific arginine residues in 4-cell blastomeres correlate with developmental potential in a way that suggested that this epigenetic modification might predispose blastomeres to contribute to the pluripotent cells of the ICM. This prediction was confirmed by the finding that when the H3-specific arginine methyltransferase, CARM1, was overexpressed in individual blastomeres, it directed their progeny to contribute to the ICM. This suggests that arginine methylation of H3 contributes to development of the ICM and identifies this modification as the earliest known epigenetic marker in the process.
03 - 07 May 2008
European Society of Endocrinology