Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1.
The interplay between hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha function and its associated mechanisms. HDAC4 and HDAC5 enhanced transactivation by HIF-1alpha without stabilizing HIF-1alpha. HDAC4 and HDAC5 physically associated with HIF-1alpha 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-1alpha to FIH-1 decreased, whereas binding to p300 increased. These results indicate that HDAC4 and HDAC5 increase the transactivation function of HIF-1alpha by promoting dissociation of HIF-1alpha from FIH-1 and association with p300.
Seo
Hee-Won
HW
College of Pharmacy, Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.
Kim
Eun-Jin
EJ
Na
Hyelin
H
Lee
Mi-Ock
MO
D002460:Cell Line; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D006899:Mixed Function Oxygenases; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D050880:p300-CBP Transcription Factors; C400300:HDAC4 protein, human; C404500:HDAC5 protein, human; D006655:Histone Deacetylases