The yin and yang of pioneer transcription factors: Dual roles in repression and activation

Pioneer transcription factors, by virtue of their ability to target nucleosomal DNA in silent chromatin, play crucial roles in eliciting cell fate decisions during development and cellular reprogramming. In addition to their well-established role in chromatin opening to activate gene expression programs, recent studies have demonstrated that pioneer factors have the complementary function of being able to silence the starting cell identity through targeted chromatin repression. Given recent discoveries regarding the repressive aspect of pioneer function, we discuss the basis by which pioneer factors can suppress alternative lineage programs in the context of cell fate control. The dual role of a pioneer transcription factor has emerged. Over the last several years, multiple studies have revealed that, upon its expression, a pioneer factor represses genes associated with a starting cell type. Then, it executes its canonical role, namely activating the expression of genes associated with a new cell type, which are originally embedded in closed chromatin. image