Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts

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Figure 4.
Figure 4.

Differential cofactor interactions characterize ERBS subtypes. (A) Transcription factor footprinting scores in MCF-7 cells treated with vehicle or E2 (45 min), averaged across ERBS subgroups for 964 motifs. Linear regression slopes (m), correlation (R), and P-values indicate changes upon E2 treatment. (B) Dot plot of top 20 enriched motifs at ERBS. Dot size reflects motif frequency; color indicates the –log10(adj.P-value). Selected Forkhead motifs (FOXA2, FOXA3, FOXP1, and FOXP2) were excluded to reduce redundancy. (C) 3D-plot of χ2 test residuals for overlap of 280 ReMap2022 ChIP-seq data sets. Residuals indicate deviation from expected distribution among the three ERBS subgroups. Colors represent the –log10 of the P-value from the χ2 test. ChIP-seq data sets and statistics are provided in Supplemental Table 6. (D) Bar plots showing overlap of top coregulators with induced (top) and constitutive (bottom) ERBS. (E) Heat map of 280 coregulator ChIP-seq data sets (x-axis) binding across induced ERBS (y-axis). Green indicates binding of the coregulator at the given induced ERBS; white indicates absence of binding. A high-occupancy cluster is indicated by a red line (bottom left). (F) Percentage overlap of ERBS subgroups with coregulators from the red cluster in E.

This Article

  1. Genome Res. 35: 1530-1543

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