Fig. 1: Paired expression and chromatin accessibility time-series data reveal the regulatory landscape for high altitude adaption.
From: Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation
a Experimental design diagram for adaptive and wildtype population choosing, individual selection by EPAS1/EGLN1 genotypes, HUVEC cell culture, time-series hypoxia induction, and multi-level omics data profiling. b Hierarchical clustering of gene expression (left panel) and chromatin accessibility (right panel) indicates hypoxia is a multi-stage biological process. Gene expression profiles group 0 h, 6 h, and 1 day as the first stage, and 3 day and 5 day as the second stage. Chromatin accessibility responses earlier to hypoxia than gene expression by further dividing the first stage into two sub-groups (0 h and 6 h, and 1 day). c Unsupervised principal component analysis for 12,998 genes (upper panel) and 51,406 HUVEC enhancers (lower panel). In all, 6 h and 1 day cells tend to be similar under hypoxia pressure and 0 h, 3 day, and 5 day samples present large variation at both chromatin accessibility and gene expression. Accessibility pattern shows a more smoothed trajectory than expression. d TF response to hypoxia by their enriched motifs and gene expression dynamics across time points. e Tibetan samples show the blunted responses to hypoxia by the number of differentially expressed genes (DEGs) between adjacent time points. DEGs are identified by limma with FDR control 0.05. f Positively selected SNPs for high altitude adaptation quantified by the CMS score thresholding by −log10(p-value) are enriched in the open regions revealed by HUVEC ATAC-seq data but not in embryonic stem cells (ESC). P-value of CMS score for each SNP were calculated by Fisher’s method (“Methods” for details). Error bars indicate the mean ± standard error of fold change between replicates (n = 10 biologically independent samples). Source data are provided as a Source data file.
