Pioneer factors outline chromatin architecture

Pioneer factors are transcription factors capable of binding to nucleosomal DNA, initiating chromatin opening, and facilitating gene expression. By overcoming nucleosomes, pioneer factors enable cellular reprogramming, tissue-specific gene expression, and genome response to external stimuli. Here we discuss the recent literature on how pioneer factors modulate chromatin architecture at multiple levels, from local chromatin accessibility to large-scale genome organization, including chromatin compartments, topologically associating domains, and enhancer-promoter looping. Understanding the mechanisms by which pioneer factors modulate chromatin organization dynamics is key to understand their broader impact on gene expression regulation.