Figure 7.

UF-enriched super-enhancer chr16: 69412415–69482923 up-regulates three UF-induced anti-oxidant genes NQO1, CYB5B, and WWP2 in HAECs. (A) The genome track of chr16:69412415–69482923 (hg19), a UF-enriched super-enhancer where the H3K27ac signal is increased in HAECs under UF (blue) compared with DF (red). CVD SNP rs75086474 is labeled by an asterisk (*). PCHi-C in HAECs suggested physical interactions between chr16: 69412415–69482923 and the promoters of NAD(P)H:quinone oxidoreductase 1 (NQO1), Cytochrome B5 Type B (CYB5B), and WW Domain Containing E3 Ubiquitin Protein Ligase 2 (WWP2). (B) Increased transcriptional levels of NQO1, CYB5B, and WWP2 in HAECs in HAECs under UF compared with those under DF. (C) CRISPR interference targeting the SNP rs75086474-surrounded H3K27ac peak reduced the mRNA expression of NQO1, CYB5B, and WWP2 in HAECs cultured under UF. (n = 7–10). (D) CRISPR activation targeting the SNP rs75086474-surrounded H3K27ac peak increased the mRNA expression of NQO1, CYB5B, and WWP2 in HAECs. (n = 4–6). (E) CRISPR activation targeting the SNP rs75086474 significantly increased the protein expression of NQO1 and WWP2 in HAECs. (n = 3–4). Data represent mean ± SEM. *adjusted P value ≤0.05 and **adjusted P value ≤0.01 were determined by two-sided Student’s t test. Source data are available for this figure: SourceData F7.