Table 1.
Potentially functional antioxidant response elements (ARE) on Nrf2-dependent acute lung injury (ALI) genes determined in a neonate mouse model.
| Gene Symbol |
Gene Title | PWM | MS | Distance to Transcription Start Site |
*Data Source |
† FD (Baseline) or Trend/p value (Hyperoxia) |
|---|---|---|---|---|---|---|
| Akr1b8 | aldo-keto reductase family 1, member B8 | 19.4, 13.7 |
0.922, 0..934 | −3742, −4012 | P2 | −2.0 |
| Days 1–2 | Low (0.001/ 0.002) | |||||
| Aox1 | aldehyde oxidase 1 | 15, 12.6 | 0.943, 0.836 | −323, −225 | P1-P4 | −2.3/−2.7/−2.4/−2.1 |
| Day 3 | Low (0.001) | |||||
| Atp1b1 | ATPase, Na+/K+ transporting, beta 1 polypeptide |
15.3, 12.1 | 0.917, 0.891 | −972, −817 | P3 | 2.4 |
| Birc6 | baculoviral IAP repeat-containing 6 | 13.9 | 0.877 | −800 | P2 | −2.0 |
| Bscl2 | Bernardinelli-Seip congenital lipodystrophy 2 homolog |
18.7, 11.7 | 0.947, 0.843 | 204, −4499 | Day 3 | Low (0.009) |
| Cbr3 | carbonyl reductase 3 | 14.1 | 0.875 | −736 | Day 3 | Low (0.003) |
| Cdca7 | cell division cycle associated 7 | 11 | 0.795 | −2462 | P3 | −2.3 |
| Cltc | clathrin, heavy polypeptide (Hc) | 15.2–10.9 | 0.935–0.797 | −1984, −1307, −1795, −542 | Day 1 | Low (0.017) |
| Cyb5a | cytochrome b-5 | 18.5–13 | 0.952–0.895 | −2308, −2742, −1836 | Day 3 | Low (0.007) |
| Egr1 | early growth response 1 | 11.9 | 0.839 | −3334 | P3 | −2.7 |
| Ehd1 | EH-domain containing 1 | 11.5 | 0.89 | −3075 | Day 2 | High (0.001) |
| Eif4g2 | eukaryotic translation initiation factor 4, gamma 2 |
13.7 | 0.893 | −644 | Day 2 | High (0.001) |
| Fgfbp1 | fibroblast growth factor binding protein 1 | 14.5 | 0.942 | −1238 | Day 3 | Low (0.003) |
| Fkbp5 | FK506 binding protein 5 | 15 | 0.931 | −4611 | P3 | 2.2 |
| Ftl1 | ferritin light chain 1 | 20.7 | 0.981 | −1087 | Day 2 | Low (0.002) |
| Gclc | glutamate-cysteine ligase, catalytic | 21.6 | 0.99 | −3795 | Days 1–2 | Low (0.005/0.004) |
| Glipr1 | subunit GLI pathogenesis-related 1 (glioma) | 12.5 | 0.884 | −3418 | Day 2 | Low (0.003) |
| Gsta3 | glutathione S-transferase, alpha 3 | 12.9 | 0.86 | −126 | P1, P3, P4 | −4.9/−4.8/−5.3 |
| Hexa | hexosaminidase A | 13, 10.5 | 0.836, 0.81 | −2057, −1779 | Day 2 | Low (0.01) |
| Hmox1 | heme oxygenase (decycling) 1 | 19.3–10.8 | 0.968–0.862 | −3873, −3925, −3201 | Day 2 | Low (0.002) |
| Hsp90aa1 | heat shock protein 90, alpha (cytosolic), class A member 1 |
16.3, 10.3 | 0.947, 0.867 | −2986, −4958 | Day 2 | High (0.005) |
| Hspa8 | heat shock protein 8 | 13 | 0.904 | −1158 | Day 1 | High (0.027) |
| Htatip2 | HIV-1 tat interactive protein 2, homolog | 16.4 | 0.954 | −54 | Day 3 | Low (0.003) |
| Ift80 | intraflagellar transport 80 homolog | 10.8 | 0.851 | −3728 | P3 | −2.6 |
| Day 2 | Low (0.003) | |||||
| Il6 | interleukin 6 | 18.3 | 0.965 | −256 | Day 2 | Low (0.007) |
| Kif5b | kinesin family member 5B | 10.6 | 0.907 | −1043 | P1-P4 | 2.6/2.9/2.8/2.7 |
| Malat1 | metastasis associated lung | 15.3 | 0.904 | −4261 | P3 | −2.0 |
| Mcm5 | minichromosome maintenance deficient 5, cell division cycle 46 |
10.2 18 | 0.829 | −750 | P3 | −2.4 |
| Me1 | malic enzyme 1, NADP(+)-dependent, cytosolic |
18 | 0.944 | 8 | Days1, 3 | Low (0.001/0.003) |
| Mki67 | antigen identified by monoclonal | 11.8 | 0.849 | −740 | P3 | −2.3 |
| Nek6 | NIMA (never in mitosis gene a)-related expressed kinase 6 |
18 | 0.967 | −4345 | Day 2 | High (0.004) |
| Nfat5 | Nuclear factor of activated T-cells 5 (Nfat5), transcript variant a, mRNA |
10.3 | 0.896 | −928 | P2 | −2.2 |
| Nqo1 | NAD(P)H dehydrogenase, quinone 1 | 16.4 | 0.87 | −422 | Day 3 | Low (0.003) |
| Oasl2 | 2’-5’ oligoadenylate synthetase-like 2 | 10.7 | 0.883 | −61 | P2 | 2.3 |
| Pgd | phosphogluconate dehydrogenase | 18.6, 11.7 | 0.971, 0.808 | −4145, −4177 | Day 1 | Low (0.03) |
| Pir | pirin | 20, 12.6 | 0.958, 0.909 | 118, −219 | Day 1 | Low (0.007) |
| Pola1 | polymerase (DNA directed), alpha 1 | 12.5 | 0.872 | −3001 | P3 | −2.5 |
| Prdx1 | peroxiredoxin 1 | 15.7–14.9 | 0.923–0.937 | −138, −2451, −4889 | Day 2 | Low (0.001) |
| Rrm2 | ribonucleotide reductase M2 | 16.2 | 0.947 | −3190 | P3 | −2.4 |
| Slc7a11 | solute carrier family 7 (cationic amino acid transporter, y+ system), member 11 |
14.1 | 0.843 | −99 | Day 3 | Low (0.007) |
| Sord | sorbitol dehydrogenase | 11.8 | 0.899 | −4245 | P1 | −2.0 |
| Srxn1 | sulfiredoxin 1 homolog | 12.7 | 0.862 | −50 | Days 2–3 | Low (0.004/0.004) |
| Timp1 | tissue inhibitor of metalloproteinase 1 | 13 | 0.877 | −1957 | Day 1 | Low (0.04) |
| Tlcd2 | TLC domain containing 2 | 13.7 | 0.877 | −4977 | P1 | 2.1 |
| Day 3 | High (0.002) | |||||
| Tomm20 | Translocase of outer mitochondrial membrane 20 homolog |
10.3 | 0.915 | −131 | Day 2 | Low (0.002) |
| Txnl1 | thioredoxin-like 1 | 13.1 | 0.9 | 45 | Day 2 | Low (0.001) |
| Txnrd1 | thioredoxin reductase 1 | 17.9, 10.6 | 0.928, 0.84 | −97, −403 | Days 1–3 | Low (0.005/0.001/0) |
| Ubc | ubiquitin C | 12.7, 10.6 | 0.907, 0.871 | −1794, −254 | Days 1, 3 | Low (0.009/0.003) |
| Wac | WW domain containing adaptor with Coiled coil |
16.8 | 0.873 | −3912 | P2 | −2.2 |
ARE, antioxidant response element. PWM, position weight matrix. MS, matrix significance.
¶
Selected bound AREs determined by mouse ChIP-seq analyses [21–24] with PWM greater than 10 in 5’-untranslated region (UTR) and 5 kb promoter of the genes are shown. Expanded data for full gene list and ARE search in Appendices A and B. †Fold difference at baseline (postnatal days P1, P2, P3, or P4) or expression trend and p value during hyperoxia exposure (Days 1, 2, or 3) in Nrf2−/− neonates compared to Nrf2+/+ neonates.
*
Microarray analyses data sources of the Nrf2-dependent genes - baseline (P1-P4) or during hyperoxia (Days 1–3).