title: Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1.
abstract: 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.
authors.affiliation: College of Pharmacy, Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hee-Won
authors.initials: HW
authors.lastname: Seo
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyelin
authors.initials: H
authors.lastname: Na
authors.forename: Mi-Ock
authors.initials: MO
authors.lastname: Lee
mesh_terms: 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*
chemical_list: 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