Extended Data Fig. 2: Chromatin accessibility and transcriptional changes upon HHEX deletion.
a,b, Bar graph and volcano plot showing the number (a) and adjusted P value distribution (b) of differential peaks in KO cells compared to WT. Differential ATAC peaks were identified by DESeq2 using default parameters. FDR < 0.05 are counted as one significant peak. Less accessible peaks in KO are marked in blue and more accessible peaks in KO in orange. The number of differential peaks is indicated. c,d, TF motif enrichment in cluster I (c) and II (d) regions. One-sided hypergeometric test was used to compare the enrichment of proportions of TF motifs for each cluster (foreground ratio) versus those for total atlas (background ratio). The horizontal axis shows the binomial Z-score, representing the number of standard deviations between the observed count of each cluster peaks containing a TF motif and the expected count based on the background ratio. The P values are provided in Supplementary Table 3. e, IGV tracks (average of two independent experiments) show chromatin accessibility at representative liver genes loci identified in cluster III. Scale bar, 5 kb. f, Top 7 mouse phenotypes associated with the regulatory regions identified in cluster III. The term of mouse phenotypes was selected based on the rank of binomial test and cut-offs of region fold enrichment >1.4 and observed regions >80. The P values are indicated. g,h, Flow cytometry analysis (g) and quantification (h) of HNF4A+ cells at DE, GT, and PP1 stages. Each symbol represents one independent experiment (n = 4 independent experiments) and data are presented as mean ± s.d. Statistical analysis was performed using unpaired two-tailed Student’s t-test. Data shown in a-f are from two independent experiments.
