1. N H N H Figure S1 parp-1 +/+ parp-1 -/- HIF-2 DAPI
Fig S1. Nuclear HIF-2 accumulation by hypoxia is reduced in parp-1 -/- immortalized MEFs. Immunofluorescence staining of parp-1 +/+ and parp-1 -/- immortalized MEFs incubated in normoxia (N) or hypoxia (H, 16 hours at 1 % O2). Representative images from several independent experiments are shown. 1

2. Figure S2 H H
Control
PARP-1
siRNA:
Control
siRNA:
HIF-2α
siRNA:
Control
HIF-1α
PARP-1
HIF-2α
HIF-1α
β-Actin
β-Actin
β-Actin
Figure S2. Validation of silencing efficacy: siRNA of PARP-1, HIF-2 or HIF-1. (Cells were transfected with the correspondig siRNAs and 48h later, the expression levels of the targeted protein was evaluated by WB. HIF expression was analyzed after 16 hours of exposure to hypoxia (1% O2). 2

3. Figure S3 15 75
parp-1+/+ 15
Liver
Kidney
Brain
parp-1-/- 10 50 10
Epo mRNA expression
(fold induction) * 5 25 5 ** N H N H N H
Figure S3. EPO mRNA levels were determined by Q-PCR from liver, kidney and brain . The level of mRNA in each sample was expressed as fold of the value in control wild-type mice. Numeric value represents mean of hypoxic
induction in each genotype at 8 hours, respectively. (*) and (**) indicate p< 0.05 and p<0.001, with respect to wild-type mice. 3