Epigenetic modifications in pluripotent and differentiated cells.

Epigenetic modifications constitute a complex regulatory layer on top of the genome sequence. Pluripotent and differentiated cells provide a powerful system for investigating how the epigenetic code influences cellular fate. High-throughput sequencing of these cell types has yielded DNA methylation maps at single-nucleotide resolution and many genome-wide chromatin maps. In parallel to epigenome mapping efforts, remarkable progress has been made in our ability to manipulate cell states; ectopic expression of transcription factors has been shown to override developmentally established epigenetic marks and to enable routine generation of induced pluripotent stem (iPS) cells. Despite these advances, many fundamental questions remain. The roles of epigenetic marks and, in particular, of epigenetic modifiers in development and in disease states are not well understood. Although iPS cells appear molecularly and functionally similar to embryonic stem cells, more genome-wide studies are needed to define the extent and functions of epigenetic remodeling during reprogramming.