Figure 2.

Cohesin haploinsufficiency induces loss of interactivity of promoter-enhancers at tumor suppressor genes. (A) Correlation plot between the compartment c-scores of Smc3/Bcl6 versus Bcl6 tumor cells at 100kb resolution. (B) Correlation plot for the change in compartment c-scores of Smc3/Bcl6 versus Bcl6 tumor cells and the change in compartment c-scores of Smc3^{wt /–} versus Smc3^{wt /wt} centrocytes (CC) at 100kb resolution. (C) Correlation plot for the log₂ normalized loop interactivity of Smc3/Bcl6 versus Bcl6 tumor cells at 20kb resolution. (D) Correlation plot for the log₂ fold change of normalized loop interactivity of Smc3/Bcl6 versus Bcl6 tumor cells and the log₂ fold change of normalized loop interactivity of Smc3 ^wt/– versus Smc3 ^wt/wt centrocytes (CC) at 20kb resolution. (E) Virtual 4C analysis showing normalized interactions with the Tet2 promoter for Bcl6 tumors (blue line) and Smc3/Bcl6 tumors (red line) at 20kb resolution. Loop calling significance following the mango approach are shown for Bcl6 and Smc3/Bcl6 tumors with –log₁₀(FDR). Enhancers were defined as H3K27Ac peaks mapped in germinal center B cells by Mint-ChIP. Rad21 ChIP-seq was performed in the mouse lymphoma cell line CH12.LX (35). The differences between normalized interactions with the Tet2 promoter are shown as log₂ fold-change between Bcl6 and Smc3/Bcl6 tumors. (F) RT-qPCR for Tet2 mRNA in Bcl6 (n=3) and Smc3/Bcl6 (n=3) tumors, normalized to Hprt1 mRNA expression.