Embryonic stem cell identity is specified by a network that principally involves the transcription factors Oct4, Sox2, and Nanog. Adult somatic cells can be reprogrammed to pluripotent embryonic stemlike cells by overexpressing certain transcription factors in this network (1). It has been suggested that embryonic stem cells represent a “ground state” for a mammalian cell based solely on the activities of these transcription factors and a “freedom” from extrinsic signals for cell differentiation (2).

Chromatin—the DNA and proteins that comprise chromosomes—might also affect this ground state as its components include fundamental regulators of development. Indeed, chromatin in embryonic stem cells differs from that in lineage-restricted cells in several respects. Embryonic stem cell chromatin is decondensed, such that major structural proteins, such as histone H1, are loosely bound and exhibit hyperdynamic binding kinetics (3). High expression levels of Polycomb-group repressor proteins and methylation of histone 3 (H3) on a specific lysine (K27) are present, most notably associated with silenced developmental gene loci (4, 5). These target loci also exhibit features of active chromatin (regions where DNA is being transcribed into RNA), including histone 3 methylation on lysine 4, which may ready genes for subsequent expression (6, 7). Despite its unique properties, the function of chromatin in embryonic stem cells remains uncertain. Embryonic stem cell lines that lack critical chromatin regulators, including DNA methyltransferases, histone methyltransferases, chromatin-remodeling proteins, and Polycomb-group proteins (8), tend to exhibit defective differentiation, which may reflect roles for these components in differentiation-