Figure 4. Perturbing cellular Zn²⁺ causes global changes in TF motif enrichment.

(A) TFEA MA plots showing enrichment scores of 880 TF motifs. Cells were either treated with 50 μM TPA (left) or 30 μM ZnCl₂ (right) for 30 mins, and enrichment scores (E-scores) were calculated relative to untreated control cells. A positive E-score denotes enrichment of the motif relative to the center of the ATAC-seq peak while a negative E-score denotes depletion of the motif. Motifs with a p_adj ≤ 1E-6 are colored blue. (B) E-scores for ZnCl₂-treated cells vs TPA-treated cells show a strong negative correlation. Colors denote TF motifs that were significant (p_adj ≤ 1E-6) in both conditions, one condition only, or neither condition. (C) Venn diagrams denoting the number of TF motifs that were significantly enriched or depleted in each treatment. Overlap indicates the TF motifs whose enrichments were inverted between treatments. (D) Left, DAVID tools analysis showing that motifs with a significant positive enrichment in ZnCl₂ and a significant depletion in TPA are enriched for Zn²⁺ fingers relative to the background (all 880 TF motifs). Listed annotations are the top 15 annotations with a FDR < 0.1. Right, annotations with a FDR < 0.1 for TF motifs that were enriched with TPA and depleted in ZnCl₂.