HUVEC cells fixed and protein-DNA complexes crosslinked by treatment with 1% formaldehyde, and then quenched with glycine (125mM). Next, cells were washed 3 times with ice-cold PBS, collected using a cell scraper and resuspended in ice-cold lysis buffer (1% SDS, 10 mM EDTA, 50 mM Tris-HCl pH 8.1). DNA was sheared by using a sonicator (Diagenode Bioruptor, Belgium). Samples were diluted 1/10 with dilution Buffer (0.01% SDS, 1.1% Triton X-100, 1.2 mM EDTA, 16.7 mM Tris-HCl pH 8.1, 167 mM NaCl) and then precleared with Salmon Sperm DNA/Protein A agarose 50% slurry (Fast Flow, Millipore, 16-156.) Sample were immunoprecipitated with different antibodies at 4°C rocking overnight; HIF1A (PM14), EPAS1 (PM9),  ARNT (Novus NB-100-110) and pre-immune serum used as negative control.Immunocomplexes were recovered by addition of Salmon Sperm DNA/Protein A agarose 50% slurry. Then samples were sequentially washed in Low Salt Wash Buffer (0.1% SDS, 1% Triton X-100, 2 mM EDTA, 20 mM Tris-HCl pH 8.1, 150 mM NaCl), High Salt Wash Buffer (0.1% SDS, 1% Triton X-100, 2 mM EDTA, 20 mM Tris-HCl pH 8.1, 500 mM NaCl), LiCl buffer (0.25 M LiCl, 1% NP-40, 1% NaDesoxycholate, 1 mM EDTA, 10 mM Tris-HCl pH 8.1), and twice in TE buffer (10 mM Tris-HCl pH 8, 1 mM EDTA). Elution of protein-bound DNA was performed using 500 µl of fresh elution buffer (1% SDS, 0.1 M NaHCO3). Next crosslinking of all samples was reversed by the overnight incubation with 200 mM NaCl at 65°C. Next day, proteins were removed by the addition of 10 µl of 0.5 M EDTA, 20 µl Tris-HCl pH 6.5 and proteinase K (40 µg/sample). Then immunoprecipitated DNA was purified by Phenol:Chloroform:Isoamyl alcohol extraction and ethanol precipitation (UltraPure™ phenol:Chloroform:Isoamyl Alcohol 25:24:1, Invitrogen, 15593-031). Libraries were prepared according to Illumina ChIP-Seq kit's intructions (Illumina, IP-202-1012).