Abstract
TrxG and PcG complexes play key roles in the epigenetic regulation of development through H3K4me3 and H3K27me3 modification at specific sites throughout the human genome, but how these sites are selected is poorly understood. We find that in pluripotent cells, clustered CpG-islands at genes predict occupancy of H3K4me3 and H3K27me3, and these "bivalent" chromatin domains precisely span the boundaries of CpG-island clusters. These relationships are specific to pluripotent stem cells and are not retained at H3K4me3 and H3K27me3 sites unique to differentiated cells. We show that putative transcripts from clustered CpG-islands predict stem-loop structures characteristic of those bound by PcG complexes, consistent with the possibility that RNA facilitates PcG recruitment or maintenance at these sites. These studies suggest that CpG-island structure plays a fundamental role in establishing developmentally important chromatin structures in the pluripotent genome, and a subordinate role in establishing TrxG/PcG chromatin structure at sites unique to differentiated cells.