Fig. 4: FOXA1 is extensively redistributed at lineage-specific regulatory elements. | Nature Communications

Fig. 4: FOXA1 is extensively redistributed at lineage-specific regulatory elements.

From: Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer

Fig. 4: FOXA1 is extensively redistributed at lineage-specific regulatory elements.

a Normalized ChIP-seq tag density for FOXA1 at NEPC-enriched and PRAD-enriched FOXA1-binding sites under the indicated conditions. Profile plots (top) represent mean tag density at sites depicted in the heatmaps. b Enrichment of FOXA1 peaks for overlap with NEPC-enriched and PRAD-enriched FOXA1-binding sites in the indicated conditions, normalized to FOXA1 peaks shared between PRAD and NEPC. cf Normalized ChIP-seq tag density for H3K27ac (c) and FOXA1 (e) at Ne-CREs and Ad-CREs under the indicated experimental conditions. Enrichment of overlap of H3K27ac peaks (d) and FOXA1 peaks (f) with Ne-CREs and Ad-CREs under the indicated conditions. gh Normalized ChIP-seq tag density for ASCL1, FOXA1, and H3K27ac under the indicate experimental conditions at NEPC-enriched FOXA1 sites (g) and Ne-CREs (h). i Effect of ASCL1 overexpression on transcript levels of indicated genes, measured by qPCR. Fold-change relative to +GFP condition is shown, using normalization to GAPDH. Three biological replicates are shown for each condition. jk Gene set enrichment analysis of genes upregulated at least 8-fold in LuCaP NEPC (j) or PRAD (k) at adjusted p-value < 10−18. Genes are ranked by differential expression between LNCaP + ASCL1 + NKX2-1 and +GFP conditions based on RNA-seq. Unadjusted permutation-based one-sided p-values for enrichment are shown. Source data are provided as a Source Data file.

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