(a) Mediator-recruited Cohesin complexes orchestrate cell-type specific enhancer-promoter loops, providing a mechanism for the cell-type specific action of an enhancer on a given promoter and, by extension, cell-type specific gene expression patters. In ESCs, many Oct4 (O), Sox2 (S), and Nanog (N) bound regions of the genome coincide with Mediator and Cohesin occupancy, indicating that these transcription factors recruit mediator to enhancers and promoters. (b) In fibroblasts, where OSN are not expressed, Mediator and Cohesin show differential DNA binding patterns and enhancer-promoter looping events at ESC-specific gene loci are absent.