Histone H4K20me3 and HP1α are late heterochromatin markers in development, but present in undifferentiated embryonic stem cells

We report here that the formation of heterochromatin in cell nuclei during mouse development is characterised by dynamic changes in the epigenetic modifications of histones. Our observations reveal that heterochromatin in mouse preimplantation embryos is in an immature state that lacks the constitutive heterochromatin markers histone H4 trimethyl Lys20 (H4K20me3) and chromobox homolog 5 (HP1 alpha, also known as CBX5). Remarkably, these somatic heterochromatin hallmarks are not detectable - except in mural trophoblast - until mid-gestation, increasing in level during foetal development. Our results support a developmentally regulated connection between HP1 alpha and H4K20me3. Whereas inner cell mass (ICM) and epiblast stain negative for H4K20me3 and HP1 alpha, embryonic stem (ES) cell lines, by contrast, stain positive for these markers, indicating substantial chromatin divergence. We conclude that H4K20me3 and HP1 alpha are late developmental epigenetic markers, and slow maturation of heterochromatin in tissues that develop from ICM is ectopically induced during ES cell derivation. Our findings suggest that H4K20me3 and HP1 alpha are markers for cell type commitment that can be triggered by developmental or cell context, independently of the differentiation process.