Distinct epigenomic landscapes of pluripotent and lineage-committed human cells.

There are over 200 different human cell types, each with a unique function. For example, embryonic stem (ES) cells have the unique ability to differentiate to nearly any cell type, in contrast to terminally differentiated fibroblast cells which serve the specific function of providing the structural framework of connective tissues. Despite these dramatic functional differences, both ES cells and fibroblasts share the same genome sequence. Rather, it is thought that epigenetic modifications, such as methylation of DNA and post-translational modifications of histones, contribute to the unique gene expression profile of each cell type, and therefore to unique cellular functions. But how much epigenomes differ remains unclear. Here, we confirm that epigenomic landscapes in hESCs and lineage-committed cells are drastically different. By using techniques to map various epigenetic modifications in ES cells and fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive histone modifications, which form blocks that significantly expand in fibroblasts. Our results provide new insights into epigenetic mechanisms underlying properties of ES cells and differentiation.