Structural insights into the recognition of native nucleosomes by pioneer transcription factors

Pioneer transcription factors possess the unique ability to bind to nucleosomal DNA and locally open closed chromatin, enabling the binding of additional chromatin-associated factors. These factors are pivotal in determining cell fate. Structural studies of pioneer transcription factors interacting with nucleosomes have predominantly relied on model systems incorporating canonical DNA motifs within synthetic, strongly positioned DNA. However, recent advances have revealed structures of several pioneer transcription factors bound to their native nucleosome targets at gene enhancers involved in cell reprogramming. These findings offer fresh insights into how pioneer transcription factors recognize and disrupt compact chromatin. In this review, we summarize these recent discoveries and explore their broader implications.