Fig. 5. Characteristics of the pluripotent epigenome. (A) Nuclei of undifferentiated (left) and differentiated (right) ES cells. The nucleus shrinks and the distribution of electrondense areas, mainly heterochromatin, changes dramatically when ES cells are induced to differentiate into primitive endoderm by the ectopic expression of Gata6. (Electron micrographs courtesy of Naoko Ikue and Shigenobu Yonehara.) (B) Epigenetic features of the pluripotent cell nucleus. The volume of the nucleus is larger than that of a differentiated cell as a result of the relaxed chromatin structure. Small regions of perinuclear heterochromatin exist, but most of the chromatin exists as euchromatin, bearing histone marks associated with transcriptional activity. The hyperdynamics of chromatin proteins (green) might contribute to the maintenance of euchromatin. Bivalent domains are also a feature of the pluripotent epigenome, in which active histone marks (such as H3K4me) are flanked by transcriptionally repressive histone marks (such as H3K9me).