Fig. 1: Negative regulation of HNF4A expression by liver-TEs.

a tSNE dimensional reduction analysis demonstrates heterogeneity in TE accessibility across different tumor types. b, c The heatmap displays the log-transformed ATAC-seq signal intensity of the TEs highly accessible in liver cancer samples (b) and non-malignant liver tissues (c). d The expression (GSVA score) of liver-TE-associated genes in TCGA-LIHC and ICGC-HCC liver cancer transcriptome datasets is correlated with a favorable prognosis for patients. The survival rates were compared using a two-sided log-rank test, without adjusting for multiple comparisons. n = 371 samples in TCGA-LIHC dataset, High = 236, Low = 135. n = 240 samples in ICGC-HCC dataset, High = 85, Low = 155. e Gene function enrichment analysis of liver-TE-associated genes was performed using the MSigDB gene set database and the R package Clusterprofiler. The one-sided hypergeometric test was used to assess gene set enrichment and p-values were adjusted using the Benjamini–Hochberg (BH) method. The bar plot displays the top 15 significantly enriched functional gene sets. f Schematic diagram shows the CRISPR/Cas9-mediated depletion of HNF4A-liver-TEs within HNF4A TRR. g HNF4A expression was determined by real-time PCR and Western blot assays after CRISPR/Cas9-mediated depletion of HNF4A-liver-TEs in liver cancer cells, n = 3 biological replicates. Significance was examined by a two-sided t-test, and mean ± SD was shown. The experiments were repeated three times with consistent results. h Colony formation assay demonstrated the growth-inhibitory effect of depleting HNF4A-liver-TEs, n = 3 biological replicates. Significance was examined by a two-sided t-test, and mean ± SD was shown. Source data are provided as a Source Data file.