Pluripotent stem cells are able to proliferate unlimitedly and to generate all somatic cell types, thus holding a great promise in medical applications. Epigenetic modifications are believed to play crucial roles in regulating pluripotency and differentiation. Recent genome-wide studies on mammalian systems have revealed several types of large chromatin domains which are associated with higher-order organization of the genome. The elucidation of genomic distribution and dynamics of these domains have shed light on the mechanisms underling pluripotency and lineage commitment.