Friend of GATA (FOG)-2 is a transcriptional co-repressor, which is critically involved in cardiac development and regulation of GATA-4 activity during hypertrophic growth of the heart. Since hypoxic tissue conditions are common for heart development and cardiac hypertrophic growth, the impact of hypoxia and the Hypoxia-inducible factor (HIF)-1 for FOG-2 RNA and protein expression was analyzed. FOG-2 protein and RNA expression in hypoxia is dependent on HIF-1a as demonstrated in HIF-1a+/+ and HIF—1a-/- mouse embryonic fibroblasts. HIF-1a siRNA experiments verified the HIF-dependent RNA and protein expression of FOG-2 in hypoxia. EMSA assays revealed that HIF-1a, however, does not bind to putative hypoxia responsive elements located upstream of the FOG-2 ATG start codon indicating that the HIF-1-dependent expression is not mediated by a direct transcriptional activation of the FOG-2 gene. Our data suggest that hypoxia may affect cardiac development and cardiac hypertrophic growth at least in part via a HIF-dependent regulation of FOG-2.