Erythropoietin

How does hypoxia influence the production of erythropoietin (EPO) in the kidneys?

1: Hypoxia decreases EPO production as it impairs renal function.
2: Hypoxia directly stimulates the renal cortex to produce EPO.
3: Hypoxia induces the accumulation of HIF-1𝛼, which triggers EPO synthesis.
4: Hypoxia has no significant impact on EPO production.