Cohesin recruitment to promoters and enhancers by general transcription factors and chromatin regulators

Background Cohesin is a major regulator of three-dimensional genome organization and gene expression. Cohesin binds to DNA and dynamically extrudes a DNA loop, often bringing two cis-regulatory elements physically close together. Extruding cohesin molecules can be stalled or stabilized when they encounter a CTCF insulator protein on DNA, thereby anchoring a DNA loop. However, many enhancer-promoter loops that are bound by cohesin lack CTCF and it is not clear how cohesin is recruited to these sites in the genome. Results Here, we investigate the localization patterns of cohesin, as well as general chromatin state and localization of transcription factors WDR5, SP1, and NFYA in mouse embryonic stem cells. The SP1 and NFYA transcription factors are ubiquitously expressed proteins known to regulate expression of genes associated with a variety of cellular processes, while WDR5 is a core component of multiple complexes that regulate chromatin. Cohesin co-binds promoters and enhancers with WDR5, with SP1, or with NFYA in mESCs and other cell types. Cohesin co-immunoprecipitates with WDR5, SP1, and NFYA and cohesin simultaneously binds to the same chromatin molecules with these proteins. At co-bound sites, depletion of cohesin does not alter binding of WDR5, SP1, or NFYA;, however depletion of WDR5, SP1, or NFYA decreases cohesin binding. Conclusions These results indicate that general transcription factors and chromatin regulators recruit cohesin to specific sites in chromatin and thereby serve as structural regulators of enhancer-promoter loops via the recruitment of cohesin.