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. 2024 Jan 5;31(3):498–512. doi: 10.1038/s41594-023-01181-7

Fig. 5. Rewired ER-bound interactions are associated with activation of ER target genes.

Fig. 5

a, O/E fold change enrichment of gained enhancer OEs for ER binding gained and lost following decitabine treatment (*P < 0.0001, permutation test). b, Average ER ChIP-seq signal intensity (Gar15-13 vehicle-treated and decitabine-treated tumors) at ERBS located at DNA hypomethylation-induced enhancer OEs. c, Expression of genes connected to gained ER-mediated enhancer OEs in vehicle-treated and decitabine-treated tumors. d, Browser snapshots showing the promoter-anchored interactions at the SPATA18 gene, together with the average ER ChIP-seq signal, EPIC DNA methylation, H3K27ac CUT&RUN signal, ChromHMM track and PCHi-C interaction track. Merged replicate data are shown (n = 4 biological replicates each; n = 3 biological replicates each for CUT&RUN and PCHi-C). In decitabine-treated tumors, the SPATA18 promoter displays an increased number of interactions with an upstream enhancer region, which gains ER and H3K27ac binding with decitabine treatment, concomitant with loss of DNA methylation. Expression of the SPATA18 gene was upregulated in decitabine-treated tumors (shown in Extended Data Fig. 7a). e, Browser snapshots showing promoter-anchored interactions at the SCUBE2 ER target gene, together with ER ChIP-seq, EPIC DNA methylation, H3K27ac CUT&RUN signal, ChromHMM track and PCHi-C interaction track. Merged replicate data are shown (n = 4 biological replicates each; n = 3 biological replicates each for CUT&RUN and PCHi-C). In decitabine-treated tumors, the SCUBE2 promoter displays additional interactions with a distal enhancer, which gains ER and H3K27ac binding with decitabine treatment. Expression of the SCUBE2 gene was significantly upregulated in decitabine-treated tumors (shown in Extended Data Fig. 7b). f, Browser snapshots showing promoter-anchored interactions at the B4GALT1 ER target gene, together with ER ChIP-seq, EPIC DNA methylation, H3K27ac CUT&RUN signal, ChromHMM track and PCHi-C interaction track. Merged replicate data are shown (n = 4 biological replicates each, n = 3 biological replicates for CUT&RUN and PCHi-C). In decitabine-treated tumors, the B4GALT1 promoter displays additional long-range interactions with a distal enhancer, which gains ER and H3K27ac binding with decitabine treatment. Expression of the B4GALT1 gene was significantly upregulated in decitabine-treated tumors (shown in Extended Data Fig. 7c).