Strategies transcription factors use to gain access to nucleosomal DNA*

The physical organization of all eukaryotic genomes is evolutionarily conserved. Histone protein octamers repeatedly wrap genomic DNA into nucleosomes to form long chromatin fibers. Nucleosomes and chromatin function to control accessibility of transcription factors to their DNA target sites, while transcription factors target DNA sites to active transcription by “opening up” chromatin. However, the dynamic interplay between transcription factor binding and nucleosome/chromatin DNA compaction is poorly understood at the mechanistic level. I will discuss proposed strategies for how transcription factors bind to their sites within compact chromatin, and the differences between activating and pioneering transcription factors. I will then present our recent single molecule studies on how nucleosomes have profoundly different impacts on the DNA binding and dissociation dynamics of these two types of transcription factors. Our finds provide a potential way to define the functional differences between activating and pioneering transcription factors.