To identify genes with pluripotent state-specific expression in embryonic stein (ES) cells, we compared gene expression profiles between Undifferentiated and differentiated mouse ES cells Using DNA microarrays. Among the numerous genes identified, we focused on coal specificity phosphatase 6 (DUSP6). which had previously been shown to be expressed in Undifferentiated human ES cells. We have identified and characterized a regulatory enhancer that we have termed PEDRE Chat controls pluripotent state-specific expression of DUSP6. This 82-base pair enchancer overlaps with, but is distinct form, a recently identified regulatory element that is regulated by the FGF-ERK pathway. The sequence of PEDRE is 100% identical between Moose and human DUSP6, suggesting that the molecular basis of DUSP6 gene expression Ill Undifferentiated state of ES cells is highly conserved during evolution. (c) 2008 Elsevier Inc. All rights reserved.