TABLE 1.
Hypoxia-inducible genes in WT, Hif-1α−/− and Hif-2α−/− ES cells assessed by microarray analysisa
| Category and gene (ID) | Average fold Induction
|
Description of product | ||
|---|---|---|---|---|
| WT | Hif-1α−/− | Hif-2α−/− | ||
| Section I | ||||
| Gpi1 (L09104) | 1.9 | 1.0 | 2.0 | Glucose phosphate isomerase 1 complex |
| Pgk1 (M15668) | 2.1 | 1.0 | 2.2 | Phosphoglycerate kinase 1 |
| PFK1 (J03928) | 2.3 | 1.0 | 2.2 | Phosphofructokinase, liver, B type |
| SLC2A1 (M22998) | 4.1 | 1.2 | 3.8 | Facilitated glucose transporter, member 1 |
| RTP801 (AK081046) | 2.9 | 1.0 | 3.1 | Regulated in development and DNA damage response |
| ERO1 (AA798624) | 2.5 | 1.0 | 2.5 | ERO1-like (S. cerevisiae) |
| LDH1 (M17516) | 4.2 | 1.5 | 4.0 | Lactate dehydrogenase 1, A chain |
| NDR1 (U60593) | 5.3 | 1.0 | 5.6 | N-myc downstream regulated 1 |
| ADM (U77630) | 12.2 | 1.2 | 10.6 | Adrenomedullin |
| VEGF (M95200) | 7.2 | 1.8 | 6.9 | Vascular endothelial growth factor |
| ADRP (M93275) | 5.3 | 1.0 | 5.1 | Adipose differentiation related protein |
| P4ha1 (U16162) | 4.8 | 1.0 | 3.6 | Procollagen-proline, 2-oxoglutarate 4-dioxygenase, alpha 1 |
| Bnip3 (AF041054) | 4.2 | 1.2 | 4.1 | BCL2/adenovirus E1B 19 kDa-interacting protein 1, NIP3 |
| Stra14 (Y07836) | 3.9 | 1.2 | 3.5 | stimulated by retinoic acid 14 |
| Aldo3 (AW121134) | 3.6 | 1.0 | 3.5 | Aldolase 3, C isoform |
| Ccng2 (U95826) | 4.5 | 1.0 | 3.8 | cyclin G2 |
| Ndr2 (AB033921) | 5.5 | 1.0 | 5.5 | N-myc downstream regulated 2 |
| Stc2 (AF031035) | 3.3 | 1.0 | 3.4 | stanniocalcin 2 |
| Tpi (L31777) | 1.8 | 1.0 | 1.9 | Triosephosphate isomerase |
| Tfr (X57349) | 1.9 | 1.0 | 2.1 | transferrin receptor |
| Igfbp2 (X81580) | 1.8 | 1.0 | 1.8 | insulin-like growth factor binding protein 2 |
| Section II | ||||
| Upp (D44464) | 2.1 | 1.1 | 2.5 | Uridine phosphorylase |
| (AI849432) | 2.6 | 1.0 | 2.8 | EST |
| (AW123751) | 2.0 | 1.0 | 2.1 | EST |
| Anxa2 (M14044) | 6.6 | 1.7 | 6.7 | Annexin A2 |
| PKP2 (AK049481) | 3.2 | 1.0 | 2.9 | Plakophilin 2 |
| Clcn3 (AF029347) | 2.7 | 1.2 | 2.0 | Chloride channel 3 |
| A2M (AI850558) | 8.6 | 1.0 | 7.9 | Alpha-2-macroglobulin |
| AK4 (AB020239) | 2.0 | 1.0 | 1.8 | Adenylate kinase 4 |
| Slca4 (U75215) | 3.7 | 1.0 | 3.9 | Neutral amino acid transporter |
| Flot1 (U90435) | 2.7 | 1.0 | 2.9 | Flotillin 1 |
| Rnf19 (AW12012) | 2.1 | 1.0 | 2.7 | Ring finger protein (C3HC4 type) 19 |
| Aoc3 (AF054831) | 6.3 | 1.2 | 6.1 | Amine oxidase, copper containing 3 |
| Socs3 (U88328) | 1.9 | 1.0 | 1.8 | Suppressor of cytokine signaling 3 |
| Lef1 (X58636) | 2.9 | 1.0 | 3.0 | Lymphoid enhancer binding factor 1 |
| GLK (AB027012) | 1.8 | 1.0 | 1.8 | Galactokinase |
| Flnb (AI591702) | 1.8 | 1.0 | 1.8 | Filamin, beta |
| Section III | ||||
| Ler3 (X67644) | 3.7 | 3.5 | 4.1 | Immediate early response 3 |
| Ddit3 (X67083) | 7.4 | 6.9 | 7.3 | DNA-damage inducible transcript 3 |
| Hsp70-4 (U08215) | 1.9 | 1.6 | 1.9 | Heat shock protein, 70 kDa 4 |
a
Genes induced in triplicate sets of hypoxic mRNAs obtained from WT, Hif-1α−/−, and Hif-2α−/− ES cells as determined by DNA microarray assays. Target gene induction represents hypoxic levels relative to normoxic levels of expression. Section I represents select known hypoxia-inducible genes. Section II contains novel hypoxia-inducible genes, confirmed by Northern blot analysis. Section III includes known HIF-independent hypoxia-inducible genes. ID, GenBank accession no.