Supplementary Figure 6: Vulnerability of inducible gene expression.

a) Model to illustrate the hierarchical organization of inducible gene expression. Nodes (circles) represent genes and their products, and lines (edges) indicate regulatory relationships. b) Deregulated constitutive and inducible genes after acute degradation of RAD21-TEV are enriched for cohesin binding (RAD21 peaks at baseline within 10kb of gene body, top) and for location within 40 kb of macrophage super-enhancers (bottom). Odds ratios were determined by two-sided Fisher's exact test. Meta-analysis of 3 RNA-seq experiments and 2 RAD21 ChIP-seq experiments per condition. c) Genes involved in the regulation of inducible gene expression are deregulated by cohesin cleavage in RAD21-TEV macrophages. In addition to genes and TADs, tracks show RAD21 ChIP-seq peaks, enhancers, and super-enhancers (SEs) mapped at the indicated times after LPS in wild-type macrophages. Deregulated genes are shown in black. Meta-analysis of 3 RNA-seq experiments and 2 RAD21 ChIP-seq experiments per condition. d) Features of immediate cohesin targets are diluted as more inducible genes become deregulated with time after cohesin depletion. Odds ratios and P-values (Fisher's exact test) for RAD21 binding (ChIP-seq peaks within 10kb) and enhancer proximity (super-enhancer within 40kb) of deregulated genes in RAD21-TEV and Rad21^-/- macrophages at baseline (not LPS stimulated). e) Odds ratios and P-values (Fisher's exact test) for the genomic enrichment of inducible genes²³ within 40kb of ('near') enhancers²², inducible enhancers, LPS-induced H3K27ac signal of log₂ FC >1.5 ('strongly inducible') enhancers, or super-enhancers.