Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites

Transcription factors (TFs) are proteins that bind to short DNA sequences, and control expression of genes. During cell division, TFs are removed from chromatin twice, during DNA synthesis, and during condensation of chromosomes in mitosis. How TFs can efficiently find their binding sites in DNA following these stages has been unclear. To address this problem, we have analyzed the binding pattern of the majority of all expressed TFs in human colorectal cancer cells. We find that binding of TFs is highly clustered, with more than 75% of all TF binding events occurring within 0.8% of the genome. The vast majority of all clusters contain cohesin, a ring-shaped protein complex that is important for transcription, and for cohesion of chromosomes during mitosis. The cohesin-bound sites are DNase I hypersensitive and depleted of nucleosomes, and binding of TFs to these regions is affected by loss of cohesin. We show that cohesin remains bound in S and M-phase synchronized cells, holding the nascent sister chromatids together at the TF cluster sites. Furthermore, cohesin remains bound to the cluster sites even when TFs are evicted in early M-phase. These results suggest that cohesin binding functions as a cellular memory that promotes re-establishment of TF clusters after DNA replication and chromatin condensation.