The focus of our research is on how the epigenome controls cell fates. One genome encodes the cellular functions for over 200 human cell types. We think the remarkable cellular specificities of different tissue/cell types within an individual are largely controlled by the epigenome. Epigenetic marks, including histone tail modifications and DNA methylation, are key identifiers of transcriptional output, and provide unique signatures of cellular identity. Using high-throughput experimental and computational technologies, we are trying to determine how the epigenome 1) confers pluripotency in hESCs and iPSCs; 2) controls transcription and cellular differentiation; and 3) provides a basis for many disease states. Similarly, we are trying to understand the consequences of epigenetic abnormalities in iPSCs. In addition, histone modifications provide a remarkable means for annotating the genome. We and others have shown that histone modifications can identify cell-specific enhancer elements, promoter elements and regions of transcribed RNAs. We are continuing to develop unique epigenetic signatures throughout the human genome to better understand the aforementioned elements, and remaining “junk” DNA.