Cell-fate transitions involve the integration of genomic information encoded by 
regulatory elements, such as enhancers, with the cellular environment. However, 
identification of genomic sequences that control human embryonic development 
represents a formidable challenge. Here we show that in human embryonic stem 
cells (hESCs), unique chromatin signatures identify two distinct classes of 
genomic elements, both of which are marked by the presence of chromatin 
regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), 
and low nucleosomal density. In addition, elements of the first class are 
distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap 
with previously characterized hESC enhancers, and are located proximally to 
genes expressed in hESCs and the epiblast. In contrast, elements of the second 
class, which we term 'poised enhancers', are distinguished by the absence of 
H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are 
linked to genes inactive in hESCs and instead are involved in orchestrating 
early steps in embryogenesis, such as gastrulation, mesoderm formation and 
neurulation. Consistent with the poised identity, during differentiation of 
hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers 
acquires a chromatin signature associated with active enhancers. When assayed in 
zebrafish embryos, poised enhancers are able to direct cell-type and 
stage-specific expression characteristic of their proximal developmental gene, 
even in the absence of sequence conservation in the fish genome. Our data 
demonstrate that early developmental enhancers are epigenetically pre-marked in 
hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory 
elements. Moreover, the wealth of new regulatory sequences identified here 
provides an invaluable resource for studies and isolation of transient, rare 
cell populations representing early stages of human embryogenesis.