Engineering cell identity: establishing new gene regulatory and chromatin landscapes

Cellular reprogramming can be achieved by ectopically expressing transcription factors that directly convert one differentiated cell type into another, bypassing embryonic states. A number of different cell types have been generated by such ‘direct lineage reprogramming’ methods, but their practical utility has been limited because, in most protocols, the resulting populations are often partially differentiated or incompletely specified. Here, we review mechanisms of lineage reprogramming by pioneer transcription factors, a unique class of transcriptional regulators that has the capacity to engage with silent chromatin to activate target gene regulatory networks. We assess the possible barriers to successful reprogramming in the context of higher-order chromatin landscape, considering how the mechanistic relationship between nuclear organization and cell identity will be crucial to unlocking the full potential of cell fate engineering.