H3K27me3 at pericentromeric heterochromatin is a defining feature of the early mouse blastocyst

Early mouse development is characterized by structural and epigenetic changes while cells progress towards differentiation. At blastocyst stage, the segregation of the three primordial lineages is accompanied by establishment of differential patterns of DNA methylation and post-translational modifications of histones, such as H3K27me3. Here, we analysed the dynamics of H3K27me3 at pericentromeric heterochromatin (PCH) during early development. We also followed the localization of EZH2 and BEND3, previously shown in ESCs to drive PRC2 to hypomethylated PCH. We show that the location of H3K27me3 at PCH, in addition to H3K9me3, is a defining feature of embryonic cells in vivo. Moreover, it may play an important role in structuring PCH and preserving genomic integrity at a time of globally relaxed chromatin. At peri-implantation stages, while DNA methylation is still low, EZH2 and then H3K27me3, leave PCH in epiblast progenitors at the time of their spatial segregation from primitive endoderm cells, while BEND3 remains there up to implantation. The comparison with stem cells (ESCs and TSCs) reveals that the epigenetic marks (i.e. H3K9me3 and H3K27me3) of PCH are reset during in vitro derivation and only partially restored thereafter. This highlights possible divergences between in vitro and “in embryo” epigenetic regulation regarding constitutive heterochromatin.