Abstract
Distinct combinations of transcription factors are necessary to elicit cell fate changes in embryonic development. Yet within each group of fate-changing transcription factors, a subset called 'pioneer factors' are dominant in their ability to engage silent, unmarked chromatin and initiate the recruitment of other factors, thereby imparting new function to regulatory DNA sequences. Recent studies have shown that pioneer factors are also crucial for cellular reprogramming and that they are implicated in the marked changes in gene regulatory networks that occur in various cancers. Here, we provide an overview of the contexts in which pioneer factors function, how they can target silent genes, and their limitations at regions of heterochromatin. Understanding how pioneer factors regulate gene expression greatly enhances our understanding of how specific developmental lineages are established as well as how cell fates can be manipulated.