Fig. 4: EPAS1’s downstream regulatory network.
From: Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation
a Extracting EPAS1’s subnetwork from the vPECA result. We extracted all the active REs with EPAS1’s motif binding link those REs with predicted TGs, and pool all the EPAS1-RE-TG triplets. In total, 621 TGs are regulated by EPAS1 via 1962 active REs. b The number of active REs for each TG follows a power-law distribution. c EPAS1’s 621 TGs are validated by the EPAS1’s RNAi knock-down experiment in HUVEC (p = 1.22 × 10−4, 56 overlap) and C166 (p = 7.80 × 10−11, 101 overlap) with hypergeometric test. d Functional enrichment of TGs reveals that angiogenesis and response to hypoxia are two important terms. P-values were calculated by hypergeometric test with Benjamini–Hochberg correction. e Core network for EPAS1’s regulation related to angiogenesis and response to hypoxia. Rectangles refer to TFs and circles are TGs. Genes with a red border are those with reported selection signals in Tibetan. Colors denote the −log10(p-value) of t-test of gene expression between A and W. f EPAS1’s target gene NRP2 shows blunted response to hypoxia at expression level. Data are presented as mean values ± standard error (n = 5). g NRP2 is differentially expressed after EPAS1 is knocked down in HUVEC and C166. P-value was calculated by one-sided t-test (n = 3). Boxplots are represented by minima, 25% quantile, median, 75% quantile, and maxima with data points. Source data are provided as a source data file.
