(A) ATAC-seq (n = 2) and RNA-seq (n = 3) in HeLa cells cultured at 21% oxygen, transfected with control siRNA and exposed to 0 h (control), 1 h and 24 h 1% oxygen (hypoxia (Hpx)). (B) Gene signature analysis. (C) Overlap between genes with differentially open chromatin regions (DOR genes) and genes with differential RNA expression (DEG) in response to hypoxia. Statistical significance was determined via Fisher's exact test, *** P < 0.001. (D) Gene list ranked from high to low fold change in chromatin accessibility in response to 24 h hypoxia. Up-regulated DOR genes are coloured yellow, down-regulated DOR genes are coloured orange. Some hypoxia up-regulated DEG and DOR genes and down-regulated DEG and DOR genes are labelled. (E) GeneSet Enrichment Analysis between 24 h hypoxia up-regulated DOR genes and a list of genes ranked from high to low 24 h hypoxia RNA expression fold change. (F) Percentage of 24 h hypoxia up-regulated DORs at intergenic regions that are active enhancers and active enhancers linked to the promoters of genes with 24 h hypoxia up-regulated RNA expression. (G) Motif enrichment analysis, top 5 enriched motifs are displayed.