Table S1. Full list of high-stringency HIF-1 binding sites

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1 Table S1. Full list of high-stringency HIF-1 HIF-1 ( Nearest gene locus 1 chr N DNAJB6 NM_ chr N NDRG1 NM_ chr Y RSBN1 NM_ chr Y ALDOA NM_ chr N CHD2 NM_ chr N C20orf175 NM_ chr N BHLHB2 NM_ chr N SNAPC1 NM_ chr Y PFKFB3 NM_ chr Y GPI NM_ chr Y QSCN6 NM_ chr N PKM2 NM_ chr Y CGA NM_ chr N FOS NM_ chr Y BCL2L2 NM_ chr N EGLN3 NM_ chr N MRPS18A NM_ chr N SLC2A3 NM_ chr Y PFKFB4 NM_ chr N EGFR NM_ chr Y PDK1 NM_ chr Y ANKRD37 NM_ chr Y C3orf28 NM_ chr N ZFAT1 NM_ chr Y ENO1 NM_ chr Y NARF NM_ chr N GPR37L1 NM_ chr Y JMJD1A NM_ chr N SEMA4B NM_ chr Y LOC NM_ chr Y GTF2IRD2B NM_ chr Y HIG2 NM_ chr Y ALKBH5 NM_ chr Y PNRC1 NM_ chr Y DARS NM_ chr N TPCN2 NM_ chr Y MTP18 NM_016498

2 HIF-1 ( Nearest gene locus 38 chr N TNS1 NM_ chr Y CLK3 NM_ chr N EGLN3 NM_ chr N ELF3 NM_ chr Y STC2 NM_ chr N SCARB1 NM_ chr N ITGA5 NM_ chr Y FUT11 NM_ chr N TMEM75 NM_ chr Y GBE1 NM_ chr Y ARRDC3 NM_ chr N AHNAK NM_ chr Y LDHA NM_ chr Y JARID1B NM_ chr N VGLL4 NM_ chr Y MLL5 NM_ chr N ZNF395 NM_ chr Y SAP30 NM_ chr N P2RY2 NM_ chr Y BHLHB2 NM_ chr N SLC8A3 NM_ chr N TFF1 NM_ chr N C14orf43 NM_ chr N KRT80 NM_ chr N MAF NM_ chr Y PLOD2 NM_ chr Y P4HA1 NM_ chr Y C9orf88 NM_ chr N EVL NM_ chr N ATP9A NM_ chr N GJA1 NM_ chr Y MAX NM_ chr Y C11orf30 NM_ chr N DNAJB6 NM_ chr Y C1orf69 NM_ chr Y DYNLL1 NM_ chr N SLC28A1 NM_ chr Y OXSM NM_ chr Y ALDOC NM_005165

3 HIF-1 ( Nearest gene locus 77 chr Y VKORC1 NM_ chr N Kua NM_ chr Y MAP1LC3B NM_ chr N JMJD2C NM_ chr N TLE1 NM_ chr Y TPD52 NM_ chr N CCNL1 NM_ chr N ZNF395 NM_ chr N ERRFI1 NM_ chr Y AKAP10 NM_ chr N FKSG44 NM_ chr N KRT19 NM_ chr N BZW1 NM_ chr N ZFAT1 NM_ chr N TMEM16F NM_ chr Y NUPL1 NM_ chr Y C8orf58 NM_ chr N TM2D3 NM_ chr N DDIT4 NM_ chr Y SIAH2 NM_ chr Y GAPDH NM_ chr N RASSF7 NM_ chr N KIAA0182 NM_ chr N PNPO NM_ chr N EGLN3 NM_ chr N PARN NM_ chr N KLHDC4 NM_ chr N PXDN NM_ chr Y SPRY1 NM_ chr Y KIAA0195 NM_ chr N WISP1 NM_ chr N PSMD6 NM_ chr Y RAPGEF6 NM_ chr N ZFP36L1 NM_ chr Y FBL NM_ chr N PKP2 NM_ chr N SLC9A9 NM_ chr Y INSIG2 NM_ chr Y C19orf50 NM_024069

4 HIF-1 ( Nearest gene locus 116 chr N TRIOBP NM_ chr N ADM NM_ chr N PFKFB3 NM_ chr N C2orf42 NM_ chr Y TMEM18 NM_ chr N DSP NM_ chr Y LOXL2 NM_ chr N PFKFB3 NM_ chr Y ANKRD37 NM_ chr Y DYRK1B NM_ chr N DAZL NM_ chr Y RDH11 NM_ chr Y ARRDC3 NM_ chr N NCOA3 NM_ chr N PRDM1 NM_ chr N DAAM1 NM_ chr Y GBE1 NM_ chr Y FNTB NM_ chr N DAB2IP NM_ chr Y DENND1A NM_ chr Y FEM1C NM_ chr Y SOS1 NM_ chr N C6orf122 NM_ chr Y HK2 NM_ chr N C11orf49 NM_ chr N SLA NM_ chr Y ILVBL NM_ chr Y DDIT4 NM_ chr N OTUD7B NM_ chr N MYL4 NM_ chr Y PBEF1 NM_ chr Y GAPDH NM_ chr N ZSWIM4 NM_ chr Y FAM13A1 NM_ chr N UTRN NM_ chr Y PGAM1 NM_ chr Y PPP1R3C NM_ chr N INHBA NM_ chr Y TRIM33 NM_015906

5 HIF-1 ( Nearest gene locus 155 chr N C1D NM_ chr N NUP210 NM_ chr Y C1orf51 NM_ chr Y SEC61G NM_ chr Y UBE1L2 NM_ chr N ZNF19 NM_ chr Y INSIG2 NM_ chr Y FBXO42 NM_ chr N GADD45B NM_ chr N HTR5A NM_ chr Y INHA NM_ chr N MICAL-L2 NM_ chr Y PDGFB NM_ chr N C1orf37 NM_ chr Y CCDC128 NM_ chr N SUMF1 NM_ chr Y C1orf51 NM_ chr Y BCAS4 NM_ chr Y PSMD6 NM_ chr Y CA9 NM_ chr Y SPAG4 NM_ chr N TRAM2 NM_ chr Y LONP1 NM_ chr Y NCOA5 NM_ chr Y FAM36A NM_ chr Y KLF10 NM_ chr Y RBPSUH NM_ chr Y BACE2 NM_ chr N HEY1 NM_ chr N TMEM88 NM_ chr Y SCD NM_ chr Y SLC35E1 NM_ chr N ZNF407 NM_ chr N ADM NM_ chr Y GOLGA1 NM_ chr N DHCR7 NM_ chr Y C3orf10 NM_ chr Y SLC31A1 NM_ chr N MGAT5 NM_002410

6 HIF-1 ( Nearest gene locus 194 chr N KCNMA1 NM_ chr N C6orf208 NM_ chr Y WSB1 NM_ chr N EGFR NM_ chr N KLRF1 NM_ chr Y SNAPC3 NM_ chr N PNMA2 NM_ chr N GRB10 NM_ chr N ARID1B NM_ chr N AKR1CL2 NM_ chr N CUTL1 NM_ chr N GPR135 NM_ chr N PTPRN NM_ chr N FBXW7 NM_ chr Y RASEF NM_ chr Y GDF15 NM_ chr Y MAML1 NM_ chr Y PVRL4 NM_ chr Y TFRC NM_ chr Y RAB6A NM_ chr N S100A10 NM_ chr Y PARD6B NM_ chr N RNF190 NM_ chr Y VDAC1 NM_ chr N CLN5 NM_ chr N DAPK2 NM_ chr N WISP1 NM_ chr N FOS NM_ chr Y DDX50 NM_ chr Y WDR54 NM_ chr N PPM1D NM_ chr N BCCIP NM_ chr N DPT NM_ chr Y CECR5 NM_ chr N BMP4 NM_ chr N NFKB2 NM_ chr N CLIC6 NM_ chr Y RIT1 NM_ chr Y S100P NM_005980

7 HIF-1 ( Nearest gene locus 233 chr Y DKFZp686I15217 NM_ chr Y LPIN3 NM_ chr Y C1orf161 NM_ chr Y RAN NM_ chr Y MPI NM_ chr Y UNKL NM_ chr N PARD6B NM_ chr Y CDC73 NM_ chr N SLC6A19 NM_ chr Y FNTB NM_ chr Y PPP1CB NM_ chr Y GLTSCR2 NM_ chr Y SLC2A1 NM_ chr N NAV1 NM_ chr N TSC22D2 NM_ chr N DNM2 NM_ chr N NT5DC1 NM_ chr Y ACOT6 NM_ chr N SERTAD2 NM_ chr N BHLHB3 NM_ chr Y GUK1 NM_ chr N IGFBP3 NM_ chr N C1orf116 NM_ chr Y PFKP NM_ chr N ZNF572 NM_ chr Y CITED2 NM_ chr Y NOL3 NM_ chr N WISP3 NM_ chr Y C9orf30 NM_ chr N MRPL14 NM_ chr N SLC22A18AS NM_ chr Y BHLHB2 NM_ chr Y PPP1R13L NM_ chr Y JMJD2B NM_ chr N PTPRB NM_ chr N AKAP12 NM_ chr Y FAM110C NM_ chr N ELL2 NM_ chr N PFDN4 NM_002623

8 HIF-1 ( Nearest gene locus 272 chr Y TPT1 NM_ chr N LOC NM_ chr Y POU2F1 NM_ chr Y RAD51L1 NM_ chr Y LRP1 NM_ chr N C3orf32 NM_ chr N MBTPS1 NM_ chr Y CTDSP1 NM_ chr N CAV1 NM_ chr N CLDN14 NM_ chr N PC NM_ chr N EVX1 NM_ chr N IRX1 NM_ chr N WISP1 NM_ chr N MAMDC1 NM_ chr N ST8SIA6 NM_ chr N SLC38A2 NM_ chr Y OXSR1 NM_ chr Y SMC2 NM_ chr Y EMP3 NM_ chr N ERRFI1 NM_ chr Y WDR89 NM_ chr Y MAPK6 NM_ chr N WDR60 NM_ chr Y FLJ16641 NM_ chr N RAI14 NM_ chr Y C3orf14 NM_ chr Y SCYL1 NM_ chr Y TMEM45A NM_ chr Y NCOA3 NM_ chr Y LOC NM_ chr Y AGPAT5 NM_ chr Y TRIM37 NM_ chr Y GLTSCR2 NM_ chr Y S100A10 NM_ chr Y C1orf27 NM_ chr Y WDR5B NM_ chr N N4BP3 NM_ chr Y PFKL NM_002626

9 HIF-1 ( Nearest gene locus 311 chr N BLCAP NM_ chr Y ALOXE3 NM_ chr N VRK1 NM_ chr Y NM_ chr Y PPP1R14B NM_ chr Y P4HA2 NM_ chr N TMEM45B NM_ chr Y ANKZF1 NM_ chr Y MAFK NM_ chr Y FLJ16641 NM_ chr Y BHLHB2 NM_ chr Y CCNG2 NM_ chr Y UPK1B NM_ chr Y MIF NM_ chr Y TFRC NM_ chr N KIAA0182 NM_ chr Y RNF126 NM_ chr Y DHRS13 NM_ chr N SLC37A3 NM_ chr Y UBE2V2 NM_ chr Y UBC NM_ chr Y DNASE1 NM_ chr Y RNF19 NM_ chr Y CRKL NM_ chr N PTPRM NM_ chr Y MTCH2 NM_ chr N FOXO1A NM_ chr N CYP1B1 NM_ chr N GARNL4 NM_ chr N NTHL1 NM_ chr Y ZC3HAV1L NM_ chr Y RUNX1 NM_ chr Y SFRS3 NM_ chr N UBE2E1 NM_ chr Y ZNF331 NM_ chr Y PPP2R1A NM_ chr N FLJ30934 NM_ chr Y WBSCR22 NM_ chr N NR4A2 NM_173173

10 HIF-1 ( Nearest gene locus 350 chr N KCTD15 NM_ chr N LOC NM_ chr Y ITFG2 NM_ chr Y PTDSR NM_ chr N NCOR2 NM_ chr Y ANGPTL4 NM_ chr N PARD6B NM_032521

11 Table S2. Full list of high-stringency HIF-2 HIF-2 ( Nearest gene locus 1 chr N DNAJB6 NM_ chr N C20orf175 NM_ chr N SEMA4B NM_ chr N TFF1 NM_ chr N NDRG1 NM_ chr Y HIG2 NM_ chr N TNS1 NM_ chr Y BHLHB2 NM_ chr N BHLHB2 NM_ chr N SLC2A3 NM_ chr N SNAPC1 NM_ chr N DNAJB6 NM_ chr N P2RY2 NM_ chr N KRT80 NM_ chr N EVL NM_ chr Y ALDOA NM_ chr N GPR37L1 NM_ chr N EGFR NM_ chr Y C8orf58 NM_ chr N PXDN NM_ chr N INHBA NM_ chr Y LOC NM_ chr N IRX1 NM_ chr N Kua NM_ chr Y GPI NM_ chr N ELF3 NM_ chr N SCARB1 NM_ chr N FOS NM_ chr N PKP2 NM_ chr N DAPK2 NM_ chr N C6orf122 NM_ chr Y ARRDC3 NM_ chr N TSC22D2 NM_ chr Y QSCN6 NM_ chr N PFKFB3 NM_ chr Y PFKFB3 NM_ chr Y CITED2 NM_006079

12 HIF-2 ( Nearest gene locus 38 chr N SLC28A1 NM_ chr N EGLN3 NM_ chr N WISP1 NM_ chr N ST8SIA6 NM_ chr N PKM2 NM_ chr N PARN NM_ chr N SEMA5B NM_ chr N HIST1H4H NM_ chr N ERRFI1 NM_ chr Y RSBN1 NM_ chr Y LDHA NM_ chr N ZFP36L1 NM_ chr Y MTP18 NM_ chr Y LOXL2 NM_ chr N ATP9A NM_ chr N TLE1 NM_ chr N PRKCA NM_ chr N GJA1 NM_ chr N JUNB NM_ chr N PSMD6 NM_ chr Y STC2 NM_ chr N DNM2 NM_ chr N SEMA4F NM_ chr Y FUT11 NM_ chr N HEY1 NM_ chr N FKSG44 NM_ chr N TMEM75 NM_ chr N KRT19 NM_ chr N EGLN3 NM_ chr N NR2F1 NM_ chr N PRDM1 NM_ chr N TGFBI NM_ chr Y CGA NM_ chr N ZNF572 NM_ chr Y KIAA0195 NM_ chr N SUMF1 NM_ chr N MCART1 NM_ chr N C14orf43 NM_ chr Y KLF10 NM_

13 HIF-2 ( Nearest gene locus 77 chr N TMEM44 NM_ chr N ITGA5 NM_ chr N DSP NM_ chr Y C3orf14 NM_ chr Y GBE1 NM_ chr N CLIC6 NM_ chr N C1D NM_ chr Y PDK1 NM_ chr N DAAM1 NM_ chr N C8orf78 NM_ chr N PAG1 NM_ chr N SYK NM_ chr N GADD45B NM_ chr Y ERO1L NM_ chr Y CRKL NM_ chr Y PDGFB NM_ chr N FBXW7 NM_ chr N PLB1 NM_ chr N ARRDC3 NM_ chr N KCNMA1 NM_ chr N ZSWIM4 NM_ chr N DPT NM_ chr Y S100A4 NM_ chr Y TF NM_ chr N ERRFI1 NM_ chr N ZFAT1 NM_ chr N TMEM75 NM_ chr N TRAM2 NM_ chr N EGFR NM_ chr N PNPO NM_ chr N DHCR7 NM_ chr N TPCN2 NM_ chr Y GAPDH NM_ chr Y P4HA1 NM_ chr Y IRF2BP2 NM_ chr Y C1orf161 NM_ chr Y CHD1L NM_ chr N DYRK1A NM_ chr N CXXC5 NM_016463

14 HIF-2 ( Nearest gene locus 116 chr N WASF2 NM_ chr N TLE1 NM_ chr N QKI NM_ chr N DDIT4L NM_ chr N LOC NM_ chr N TMEM49 NM_ chr Y KCTD11 NM_ chr Y AXUD1 NM_ chr N BZW1 NM_ chr N SLA NM_ chr N ROBO1 NM_ chr N ECE1 NM_ chr N RASSF3 NM_ chr N PNMA2 NM_ chr N C11orf49 NM_ chr Y DYNLL1 NM_ chr Y PLOD2 NM_ chr N EBF1 NM_ chr N SLC6A6 NM_ chr N TBL1XR1 NM_ chr Y FLJ16641 NM_ chr N BLCAP NM_ chr Y IL6R NM_ chr Y FLJ16641 NM_ chr Y C9orf88 NM_ chr N CYP1B1 NM_ chr Y FAM13A1 NM_ chr N SOX9 NM_ chr N E2F6 NM_ chr N HS1BP3 NM_ chr N DAZL NM_ chr N NCOR2 NM_ chr N FAM79B NM_ chr N SLC9A9 NM_ chr N SLC38A2 NM_ chr N MAF NM_ chr N RASSF7 NM_ chr N EGLN3 NM_ chr N ZNF395 NM_018660

15 HIF-2 ( Nearest gene locus 155 chr N PADI1 NM_ chr N P2RY2 NM_ chr Y BACE2 NM_ chr N IGFBP3 NM_ chr N RIPK4 NM_ chr N IFI44 NM_ chr N BBOX1 NM_ chr N KLHDC4 NM_ chr N AMZ1 NM_ chr Y RBM35B NM_ chr N LEPREL1 NM_ chr N DDIT4 NM_ chr N NM_ chr N IGFBP3 NM_ chr N FLJ41170 NM_ chr N GRHL2 NM_ chr N PODXL NM_ chr N SWAP70 NM_ chr N HS6ST3 NM_ chr N MRPS18A NM_ chr Y LOC NM_ chr N PCP4 NM_ chr N TOLLIP NM_ chr Y C3orf28 NM_ chr Y GLTSCR2 NM_ chr N BCCIP NM_ chr Y GTF2IRD2B NM_ chr N DYNLRB1 NM_ chr Y FOXA1 NM_ chr N ZNF395 NM_ chr N LOC NM_ chr N MAMDC1 NM_ chr N C6orf105 NM_ chr Y ILVBL NM_ chr N C1orf116 NM_ chr Y MLL5 NM_ chr N WASF2 NM_ chr Y RNF19 NM_ chr N RALGPS2 NM_152663

16 HIF-2 ( Nearest gene locus 194 chr Y TSKU NM_ chr N DIP13B NM_ chr N GREM2 NM_ chr Y BCAS3 NM_ chr N SLC7A5 NM_ chr N PITRM1 NM_ chr Y UBC NM_ chr N NR2F2 NM_ chr N UBE2E3 NM_ chr Y RAP2B NM_ chr N GALNT4 NM_ chr N INHBA NM_ chr N CDYL2 NM_ chr N TESC NM_ chr Y BMPER NM_ chr N KIAA0182 NM_ chr N CXCR7 NM_ chr N PARD3 NM_ chr N DPH4 NM_ chr N C6orf208 NM_ chr N CCNL1 NM_ chr N ITGB5 NM_ chr N MRPS33 NM_ chr N TRIM37 NM_ chr Y LOC51136 NM_ chr Y ENO1 NM_ chr N PHLDA1 NM_ chr N KIAA0182 NM_ chr N GPR135 NM_ chr N LOC NM_ chr N C7orf30 NM_ chr N UBXD3 NM_ chr N ETAA1 NM_ chr N TLE4 NM_ chr N FGD5 NM_ chr Y NOL3 NM_ chr N RAD23B NM_ chr Y GPRC5A NM_ chr N CUTL1 NM_181552

17 HIF-2 ( Nearest gene locus 233 chr N ACTL7B NM_ chr Y WSB1 NM_ chr Y BHLHB2 NM_ chr N ARHGAP26 NM_ chr N DST NM_ chr N C9orf50 NM_ chr Y SCD NM_ chr Y C3orf21 NM_ chr Y CBFA2T3 NM_ chr N N4BP3 NM_ chr Y BHLHB2 NM_ chr N AKR1CL2 NM_ chr N ELF3 NM_ chr N TRIOBP NM_ chr N FOXJ2 NM_ chr Y SERTAD1 NM_ chr N TMEM88 NM_ chr N P2RY2 NM_ chr N KCNK15 NM_ chr Y PFKFB4 NM_ chr N TSEN2 NM_ chr Y FLJ16008 NM_ chr N CXCR7 NM_ chr N ARRDC3 NM_ chr N P2RY2 NM_ chr N FOXL1 NM_ chr N C3orf32 NM_ chr N AIPL1 NM_ chr N UBE2E1 NM_ chr Y PPP1R3C NM_ chr Y FEM1C NM_ chr N SPIN NM_ chr N NUP210 NM_ chr N LOC NM_ chr Y ANKRD37 NM_ chr N PCP4 NM_ chr Y GAPDH NM_ chr N BACH1 NM_ chr Y KRT7 NM_005556

18 HIF-2 ( Nearest gene locus 272 chr Y GLTSCR2 NM_ chr N OLFML3 NM_ chr N SLC44A3 NM_ chr Y USP32 NM_ chr N MEF2A NM_ chr N LOC NM_ chr Y TRIM33 NM_ chr Y TRIM37 NM_ chr Y CA4 NM_ chr N NR5A2 NM_ chr N TEX14 NM_ chr N WASL NM_ chr Y LRP1 NM_ chr N AHNAK NM_ chr Y SLC45A3 NM_ chr Y RAD51C NM_ chr Y PPM1D NM_ chr Y GREB1 NM_ chr N ZNF572 NM_ chr N RNF190 NM_ chr Y USP32 NM_ chr N KCNA5 NM_ chr N HNMT NM_ chr Y CA4 NM_ chr Y PPM1D NM_ chr N FAM102A NM_ chr N FAM27L NM_ chr Y TFRC NM_ chr N EMILIN3 NM_ chr Y PPM1D NM_003620

19 Table S3. Oligonucleotides used for qpcr Binding region ID Forward primer Reverse primer beta actin ACCATGGATGATGATATCGCC GCCTTGCACATGCCGG EGLN3 positive control AGTGTCCGTTCCCAGCTCAG TAGGCACAGTAAACAGGCC 12 TATGGACAGAAGTGGGGGAG CTGCAGTGGTTTGTGCTTGT 17 GGGTGAAGGTGACAGCAAGT ACACAGACTCAACGTGCCA 18 TGTGTATGCGTGAGTCTTTGG GAGCCCCGAGCTACATTCCT 24 CTCGCTTCCCATTTCCTGT GTGTGAGTGAGCACGTGAG 65 GAGCGGCTACTTCCTACCCT ATAAAAGGGCTAACGGGCT 73 GGCGATGGCAGAGATAAGAA ACGCAGCTATTGCACAACA 76 GGATCCACTGGACAAGCAGT CACTCCTGGGACTGAGATGC 94 AGTACGCCTATTCTCGCCTG AATGAGCCCTGGTACGTGA 102 GTGAACTGTGCTTCCTTCCC GGGATAAACAAGGAGAGGG 140 CTTCTTTTCGCTTCCCTCCT CCTCTCGGTCTTCGCCTATT 155 TCAGATGAAAGATACGGGGC TAAAAAGGCCTCTCAGCAG 188 TTGTTTTCCGAACCCATCTC CGAACGGGTCACACTTTCTT 203 TCTCTTCCCTGAGGCTTGTC CTGGATCTGTGCATGGATGA 215 TGTTTGCTTTGACTACATAATT TTGTGAATCACCTCTGCAAT 216 GCAGCTGGACTCATCTCACA TTAAAAACACGTGCCTTCTG 223 CGAGCTCTGCCTCTGCTAAT TAGCAGGACAGGCAATGGT 240 ACTGAGAGACTGGGTGTGGG AAGTGGTGTGCGTGGAAAC 246 GACACCACGTTTTACTGCCC GCCACAACAACAAAGCTGT 282 CAGGAGCTGGGAACAGGTT GTCCCTCCGGGACTACAAGT 337 TGGAGAGTTGCACTTGGTCA ACCATTTGACATGTGCTGGA H1A204 GGAAACCTCTGGGTGAGACA AACCAGGGTGAAACCACAA H1A231 CGTTGAGAGATTCACAAAAGC TCCGCAATTTTCAGGAAGAC H1A453 AAGGCAAAGCACTGTGGACT AATGCCAGGTGAAAGGTTT H1A511 ACTCCAAGGTGGCATTGTTC TGATGAGCAGGAAGATGAC 2A229 GGTGGAAATTGGTTTAAAAAC ATCTTCCACCTGTGTGTCCA 2A315 GGCCTAGAACCATGGAGTGA TGGTTGCTGAGAGAGCAGT 2A323 GTGCTCCTCATGCTGTCTGA CCAGGCATTCATTTGTTCCT 2A350 ATGACTCAGCAGGGATCGAG TGAGCACCGACCTCCTATTC 2A411 CAAGTTCATTGAGATTATTGT TGTAGGTCCCATTGGCTTGT 2A595 TGTTGTTGTTGTCGTCGTCAT GAGTCGGGAGAGCATTTCA 2A693 TCGATGACTCTTGACTGTTTCC CCTGGCCACTGTTCTAGGTG 2A722 CAAACCACCGGTGTAAGTCC TTGAACATCAGCCTCCACAT 2A724 TGCTCTGTTACCCAGGCTTT CACCACTGTGCTCCAGCTT 2A751 AAAACCTGGTTGCATGCTG CATCACCCTGCGTGTGTAAT C5ORF15 GCCTGCATGATTGGGTACTA CGCTTTCGTGATCAGTCTGT CBWD1 CTTAGCGTCAAAGCCTTGCT ATGGGTTGCCTCTCATCTTG DDB2 TTTACTGGGGCTTGAACCTG CCCAGCTCGTTTTTGAGTGT TTLL2 CTCTGTATCACCCGCCTAGC TTTCACTGGGGTGAGGTAGC UGP2 GGACTGTTGGGGAAGCTTTA GACGCAAACCACGTACACA TMOD3 GGCTGGGAAGTTTGTGTGTT CCCCGCAAGCAAAAATATA SMURF2 TGCCACCCTACAATCAGACA AGGTTGACTTTTCCGGTGTG PAK7 GAAAGATGAACCGCAACCAT TGAGCAAATGTCCTGCTTCA GAGE6 GGGATCTCCCATAGGGTTCT CACAACGATTGGGAACATG ELMO2 TGTGTACATTCTTTGATGTTGG AGACGGAGTCTCGCAGTGTT ARRDC3 CCCCTGCAGTCACACACTC TTTGTCACATGGGACTCTTC ERRFI1HIFbind 1 GATTACAGGCTGGATGGCAC TGCTGCCAGACTGGTATGAG ERRFI1HIFbind 2 CAAGTGTGCACGTTTGAACC ATCTGTGGAAAGGCAGGAG ARRDC3 expression AATTCCGAAGAAGGCTTCCA CGAATGAGGTAGCGAGTGG ERRFI1 expression CCGATAACCATGGCCTACAG ATTCATCGGAGCAGATTTGG

20 Figure S1. Overlap between datasets (A & B) Gene loci identified in the HIF-1α and HIF-2α ChIP-seq analyses were ranked according to the maximum of the ChIP-seq signal. Using ChIP-chip gene sets (of varying stringency - defined the denoted z-score (MA) thresholds), the cumulative of gene loci identified in both the ChIP-seq and ChIP-chip datasets was identified, as the ChIP-seq threshold was reduced, and was plotted against the rank in the ChIP-seq analysis. Significant overlap was seen between the ChIP-seq and ChIP-chip datasets amongst the highest 1000 ChIP-seq peaks for both (A) HIF-1α and (B) HIF-2α. Beyond this the overlap fell to statistical background. The threshold (point of inflection) at which this happened was robust to the stringency with which the ChIP-chip peaks were defined. Using this threshold together with additional filters, high stringency gene sets were identified for both HIF-1α and HIF-2α ChIP-seq analyses (see methods). (C) The overlap between the set of HIF-1α gene loci defined these high stringency criteria and all HIF-2α peaks was examined as the threshold for definition of HIF-2α ChIP-seq peaks was reduced (similar to above analysis) and again showed a high degree of overlap amongst the 1000 highest HIF-2α peaks corresponding to approximately 250 common gene loci. (D) The reverse analysis using the high-stringency HIF-2α gene loci and all HIF-1α loci confirmed a comparable degree of overlap. Figure S2. ChIP-qPCR confirmation of enrichment at HIF (A) 20 HIF-1α were chosen at random from the list of high-stringency peaks. HIF-1α and pre-immune control chromatin immunoprecipitations were formed and subjected to analysis qpcr at these. The fold enrichment for the HIF-1α ChIP compared to the pre-immune antibody control ChIP are illustrated (means + standard deviation of three technical replicates). 18 out of 20 confirmed significant enrichment in the HIF-1α ChIP (Students t-test, p<0.05 after Bonferroni correction). ChIP-qPCR analysis was also formed on (B) randomly selected that bound HIF-2α, (C) identified ChIP-chip analysis but not ChIP-seq analysis. Figure S3. Overlap between HIF-α and hypoxic HIF-1β (A) Hypoxic HIF-1β ChIP-seq peaks were ranked according to peak and the overlapping with the high-stringency HIF-1α was plotted. (B) The high-stringency HIF-1α were ranked according to peak and the overlapping with the top 10,000 hypoxic HIF-1β ChIP-seq peaks was plotted. (C & D). The analysis was repeated for HIF-2α and hypoxic HIF-1β. (E) HIF-α ChIP-seq peaks were ranked according to peak and the overlapping with the top 500 hypoxic HIF-1β was plotted. (F) The top 500 hypoxic HIF-1β were ranked according to peak and the overlapping with the top 10,000 HIF-α ChIP-seq peaks was plotted. Figure S4. Ingenity Pathways network analysis of HIF- loci HIF- loci were examined for novel networks using Ingenuity Pathways Analysis software tool (Ingenuity Systems Inc, IPA ). The top pathway containing 59 focus molecules is shown. Loci shaded grey have direct HIF-, those in white are interacting. Interactions are demonstarted grey lines. Figure S5. Gene Set Enrichment Analysis of HIF-1 and HIF-2 gene loci Expression data were used, and GSEA analysis was formed as for Fig. 2. The cumulative enrichment score together with the position of the HIF- gene loci amongst the genes ranked fold regulation are plotted for (A) all high-stringency HIF-1 gene loci and (B) all high-stringency HIF-2 gene loci. (C) The log 2 fold regulation HIF-α is illustrated.

21 Figure S6. Gene Set Enrichment Analysis of HIF-2 gene loci stratified distance between site and TSS Expression data as for Fig. 2 were used. HIF-2 gene loci were stratified according to the distance to the nearest TSS into 4 sub groups and GSEA analysis formed as before. The cumulative enrichment score (ES), together with the position of the HIF- gene loci amongst the genes ranked fold regulation are plotted for (A) gene loci with the closest HIF-2 within 1 kb of the TSS, (B) between 1 kb and 10 kb of the TSS, (C) between 10 kb and 100 kb of the TSS and (D) greater than 100 kb from the TSS. (E) The log 2 fold regulation HIF-α is illustrated. Figure S7. Gene Set Enrichment Analysis of HIF-1 gene loci stratified position of site within the gene Expression data as for Fig. 2 were used. HIF-1 gene loci were stratified according to the position within the gene and GSEA analysis formed as before. The cumulative enrichment score (ES), together with the position of the HIF- gene loci amongst the genes ranked fold regulation are plotted for situated in the (A) intron, (B) exon, (C) 5' UTR (D) upstream of the TSS and (E) downstream of the TES. (F) The log 2 fold regulation HIF-α is illustrated. Figure S8. At HIF- loci the level of gene regulation is independent of the distance between the TSS and HIF- site For each HIF-1 site, the fold-regulation HIF of the nearest gene was plotted against the distance between the site and the TSS. Figure S9. Distribution of CAC motif downstream of RCGTG The frequency of CAC motifs downstream of each RCGTG motif within the HIF-1 and HIF-2 regions was plotted against the base position (R in the RCGTG is position 0). Figure S10. Location of DNAse1 hysensitivity and CpG islands around HIF- (A) HIF-1 and (B) HIF-2 were ranked according to distance up/downstream of the nearest TSS (vertical axis). Normoxic DNAse1 hysensitivity peaks were identified for MCF-7 cells using the ENCODE consortium dataset 1 for Hysensitivity Digital DNAse1. For each HIF-1 site, the position of each DNAse1 hysensitive peak (within 50 kb), relative to the centre of the HIF- region, was plotted (horizontal axis). This analysis shows two distinct patterns of enrichment. The first (Z-shaped) clustering of hysensitive peaks corresponds to enrichment of hysensitive within the core s of the neighboring genes. The second pattern (centered on 0 kb) corresponds to enrichment of hysensitive peaks at the HIF- themselves. This second pattern of enrichment of hysensitive peaks was seen across all HIF-, irrespective of their distance from the TSS, further confirming the validity of these more distant HIF-. (C& D) The same analysis was repeated for CpG islands (UCSC-cpgIslandExt), which demonstrates clustering of CpG islands at the s with relatively little at -distant HIF-.

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