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. 2021 Mar 2;12:1375. doi: 10.1038/s41467-021-21687-2

Fig. 4. Acute transcriptional output shapes the steady-state transcriptional response to hypoxia.

Fig. 4

a Qualitative overlap between genes called as upregulated in PRO-seq (90 min hypoxia) and RNA-seq data sets (24 h hypoxia). Odds ratio (OR) and p-value (p) are for two-sided Fisher’s exact test. b Distributions of HIF1A ChIP-seq enrichment signal for HIF1A peaks associated with genes upregulated in both PRO-seq and RNA-seq data sets (Acute response, pink) or RNA-seq only (Late response, teal). Horizontal spread of data points is proportional to density; boxes indicate medians and upper and lower quartiles. Number below plot indicates p-value for two-sided Mann–Whitney U test between the two distributions. c Comparison of transcription regulators with enriched targets among Acute response and Late response genes, as identified by the TRRUST module of Metascape. Heatmap color represents −log10(p-value) from hypergeometric enrichment test. d Comparison of transcription activity at 90 min hypoxia (gene body RPKM) with mRNA levels after 24 h hypoxia (RNA RPKM) for Acute response genes. Points are colored by density and selected example genes are labeled. Pearson correlation coefficient is shown in upper left, * denotes significant correlation (p < 2.2e−16). e Bubble plots showing relative transcription activity in wild-type (WT) and CDK8as/as HCT116 cells exposed to normoxia (pink) or hypoxia (blue) for CDK8-dependent glycolytic genes. Circle area corresponds to log2(RPKM) values, scaled within each data set. f Comparison of transcription activity at 90 min hypoxia (gene body RPKM) with enrichment signal (mean normalized tag counts) at TSS regions (for ENCODE project chromatin and RNAPII data) or peak regions (for HIF1A ChIP-seq data) for Acute response genes. Points are colored by density. Blue lines denote linear model fits to the data, with 95% confidence intervals in gray. Numbers in upper left are Pearson correlation coefficients, * denotes significant correlations (10% FDR). FDR-corrected p-values are as follows: H3K27ac 4.07e−29, H3K79me2 1.29e−27, H3K9me3 5.36e−2, DNaseI 3.93e−6, RNAPII 3.70e−15, H3K4me3 1.26e−7. See also Supplementary Figs. 5, 6 and Supplementary Data 5, 6.