RESUMEN
The nucleosome presents a formidable barrier to DNA-templated transcription by the RNA polymerase IImachinery. Overcoming this transcriptional barrier in a locus-specific manner requires sequence-specificrecognition of nucleosomal DNA by ‘pioneer’ transcription factors (TFs). Cell fate decisions, in turn, dependon the coordinated action of pioneer TFs at cell lineage-specific gene regulatory elements. Although it isalready appreciated that pioneer factors play a critical role in cell differentiation, our understanding of thestructural and biochemical mechanisms by which they act is still rapidly expanding. Recent research hasrevealed novel insight into modes of nucleosome-TF binding and uncovered kinetic principles by whichnucleosomal DNA compaction affects both TF binding and residence time. Here, we review progress and arguethat these structural and kinetic studies suggest new models of gene regulation by pioneer TFs.