Theoretical models for cohesin recruitment and the roles of origins and DNA replication in sister chromatid cohesion and enhancer–promoter communication. (A) Cohesin recruitment to enhancers (ENH) and promoters (PRO). The factor key is on the right. At enhancers (left), we posit that Pds5 (black) and SA (blue) recruit tripartite cohesin rings (step 1) and that Nipped-B (purple) displaces Pds5 (step 2) to load cohesin topologically (step 3). SA association with enhancers is facilitated by Pds5 (Misulovin et al. 2018) and unknown enhancer-specific proteins (gray). At promoters (right), we envision that the MED30 Mediator subunit (cyan) and the TBPH protein (orange) (Swain et al. 2016) recruit Nipped-B and Rad21 (red) without SMC1-SMC3 dimers or SA (step 1). At some frequency, Nipped-B–Rad21 complexes capture SMC1-SMC3 dimers (step 2) and SA-deficient cohesin is loaded (step 3). (B) We theorize that enhancers capture translocating MCM2-7 helicase complexes (Powell et al. 2015) to position early replication origins (left). DNA unwinding by MCM2-7 upon initiation of replication topologically captures both single-stranded templates within cohesin rings behind the nascent forks to establish sister chromatid cohesion (right). Replication forks push other SA-containing cohesin rings to be captured by neighboring promoters, facilitating enhancer–promoter communication (right).
