In mammalian embryos, DNA methylation is initialized to maximum levels in the epiblast by the de novo DNA methyltransferases DNMT3A and DNMT3B before gastrulation diversifies it across regulatory regions. Here we investigate the role of these two enzymes both in-vivo and in meso-endo embryoid bodies (MEEBs) and show that their differential activity during gastrulation is achieved via small but quantitative variation in sequence specificity.
