Cohesin facilitates nucleosome invasion by transcription factors.

Nucleosomes present a major barrier to transcription factor (TF) binding. However, a subgroup of TFs known as pioneer factors (PFs) can recognize motifs covered by nucleosomes and initiate chromatin opening. PFs also bind nucleosomal substrates with high affinity in vitro, which may facilitate their nucleosome invasion in vivo. Here, we show that LexA, a bacterial TF with poor nucleosome binding in vitro, can rapidly invade into a well-positioned nucleosome from a motif positioned at the dyad when expressed ectopically in yeast. This notable contrast between LexA binding in vitro and in vivo raises the possibility that TFs can exploit nucleosome dynamics in vivo to access occluded sites. Unexpectedly, we find that LexA-mediated chromatin opening can occur in the absence of DNA replication, chromatin remodeling, histone turnover, and a few histone chaperones. Instead, nucleosome invasion by LexA and a native PF, Cbf1, is promoted by the cohesin complex, illustrating an intriguing connection between cohesin and TF binding. Together, our results demonstrate that even nonpioneer TFs like LexA can bind and displace nucleosomes in vivo, through a process facilitated by cohesin.