Cohesin facilitates the regulated expression of genes located near enhancer elements. (A) Enhancers and super-enhancers (Supplemental Fig. S1) emerge as major determinants of cohesin-dependent gene regulation. The “Next to enhancer” category includes genes that are nearest neighbors of conventional enhancers. The “Near SE” category includes genes that are positioned within 40 kb of an SE, including genes that overlap SEs and nearest neighbors of SEs. “Next to SE” includes only nearest neighbors of SEs. “Diff. Hi-C interaction” indicates genes in 100-kb regions that interact differentially in control and Rad21-deficient thymocytes (Seitan et al. 2013). Other categories refer to promoter binding of the listed factors (TSS ± 2.5 kb). Multivariate multinomial regression analysis was done as described in Seitan et al. (2013). The statistical significance of regression model coefficients is indicated and only significant associations are shown. (B) Proximity to enhancers accounts for ∼50% of genes deregulated in Rad21-deficient thymocytes. (Enhancer) Genes that are nearest neighbors or overlap conventional enhancers; (SE) genes ±40 kb of a super-enhancer, overlapping a super-enhancer, or that are nearest neighbors of super-enhancers. (C) Cohesin is required for the regulation of genes near enhancers and super-enhancers. (Genome average) Expressed genes (17,003 genes); (Next to enhancer) nearest neighbors of conventional enhancers (3540 genes); (Overlapping enhancer) genes that overlap conventional enhancers (198 genes); (Near SE) ±40 kb of a super-enhancer (1036 genes); (Overlapping SE) overlap a super-enhancer (493 genes); (Next to SE) nearest neighbors of super-enhancers (447 genes). Additional data are shown in Supplemental Table 1.
