Extended Data Fig. 9. Dynamic expression of genes at ER-bound chromatin interactions in time-course of Decitabine treatment.

(a) Browser snapshots showing promoter-anchored interactions at the EVL ER target gene. Gar15-13 PDX Vehicle- and Decitabine-treated data tracks are overlayed with ER ChIP-seq for TAMR/MCF7 cell lines³; EPIC methylation for TAMRs; ChromHMM track and finally PCHi-C for TAMR cell line data. Merged replicate data shown (n = 4 biological replicates each for Gar15-13 and n = 2 technical replicates for TAMRs) In Decitabine-treated PDXs and TAMRs (Day-7 Decitabine), the EVL promoter displays additional interactions with enhancer region, which gains ER binding with Decitabine treatment in PDXs, concomitant with loss of DNA methylation in both PDXs and TAMRs. These ectopic interactions are lost after 28 days of recovery with recovery of DNA methylation at that locus. Expression of the EVL gene was significantly upregulated in Decitabine-treated vs. Vehicle PDXs (bottom right, RNA-seq TPM) and increased in Day-7 Decitabine TAMRs compared to Control Early and was restored in Decitabine Recovery (top right, RNA-seq TPM). (b) Browser snapshots showing promoter-anchored interactions at the MYO3B ER target gene. Gar15-13 Vehicle- and Decitabine-treated PDX data tracks are overlayed with ER ChIP-seq for TAMR/MCF7³; EPIC methylation for TAMRs; ChromHMM track and finally PCHi-C for TAMRs. In Decitabine-treated PDXs and TAMRs (Day-7 Decitabine), the MYO3B promoter displays increased number of interactions with an enhancer, which gains ER binding with Decitabine treatment in PDXs. The relative expression of the MYO3B gene increased in Day-7 Decitabine-treated TAMRs (RNA-seq TPM). Error bars indicate SD from two samples. (c) Browser snapshots showing promoter-anchored interactions at the SCUBE2 ER target gene. Gar15-13 PDX Vehicle- and Decitabine treatment data tracks are overlayed with ER ChIP-seq for TAMR/MCF7³; EPIC methylation for TAMRs, ChromHMM track and finally PCHi-C. In Day-7 Decitabine-treated PDXs and TAMRs, the SCUBE2 promoter displays additional interactions with a distal enhancer, which gains ER binding with Decitabine treatment. Expression of the SCUBE2 gene was upregulated in Day-7 Decitabine and its expression continued to increase in Decitabine Recovery. Error bars indicate SD from two samples. Merged replicate data shown (n = 4 biological replicates for Gar15-13 and n = 2 technical replicates for TAMRs).