Transcriptional activation of hypoxia-inducible factor-1α by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1

The interplay between hypoxia-inducible factor-1 alpha (HIF-1 alpha) and histone deacetylase (HDACs) have been well studied; however, the mechanism of cross-talk is unclear. Here, we investigated the roles of HDAC4 and HDAC5 in the regulation of HIF-1 alpha function and its associated mechanisms. HDAC4 and HDAC5 enhanced transactivation by HIF-1 alpha without stabilizing HIF-1 alpha. HDAC4 and HDAC5 physically associated with HIF-1 alpha through the inhibitory domain (ID) that is the binding site for factor inhibiting HIF-1 (FIH-1). In the presence of these HDACs, binding of HIF-1 alpha to FIH-1 decreased, whereas binding to p300 increased. These results indicate that HDAC4 and HDAC5 increase the transactivation function of HIF-1 alpha by promoting dissociation of HIF-1 alpha from FIH-1 and association with p300.