Deciphering how cells can exist in the diverse cellular states that make up a functional organism while carrying the same genomic information is a major challenge in biology. Transcription factors are responsible for the deposition of epigenomic modifications upon the genome that serve as instructions as to how the genome is being read in each different cell type, thus allowing the cell to adopt a specialized state. Furthermore, these instructions are highly dynamic and can change under the influence of extracellular cues presenting the cells with the ability to respond to changes in their environment.
Distal enhancers have emerged as key regulatory non-coding structures in the mammalian genome that support gene expression over long distances. We have identified a host of new enhancer regions in several different cell types and have shown that these enhancer networks are active in a cell state dependent manner and control cellular identity. Furthermore, we provided evidence that enhancers can be divided between inactive, active and poised configurations based on specific histone modifications providing insight into the limitations of a cells ability to respond to environmental cues. Therefore cellular identity can be largely described by the genome wide activity of its enhancer networks.