Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity.

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that controls expression of genes responsive to low oxygen tension, including vascular endothelial growth factor (VEGF), erythropoietin, and glycolytic enzymes. The activity of HIF-1alpha is regulated by binding to the transcriptional co-activator cAMP-response element-binding protein-binding protein (CBP)/p300. Using the yeast two-hybrid screening system, ...
we found that the inhibitory domain of HIF-1alpha strongly interacted with the C-terminal domain of histone deacetylase (HDAC) 7. The o-nitrophenyl beta-d-galactopyranoside assay revealed that regions containing amino acids 735-785 of HIF-1alpha and amino acids 669-952 of HDAC7 were minimum contact sites of the interaction. The binding of HDAC7 with HIF-1alpha was reproduced in HEK293 cells grown under normoxic and hypoxic conditions (2% O(2)). HDAC7 bound solely to HIF-1alpha among other HIF-alpha family members, including HIF-2alpha and HIF-3alpha, whereas HIF-1alpha only interacted with HDAC7 in the class II HDAC family. Although HDAC7 was localized dominantly in the cytoplasm at normal oxygen concentrations, HDAC7 co-translocated to the nucleus with HIF-1alpha under hypoxic conditions. In the nucleus, HDAC7 increased transcriptional activity of HIF-1alpha through the formation of a complex with HIF-1alpha, HDAC7, and p300. Taken together, these results indicate that HDAC7 is a novel transcriptional activator of HIF-1alpha
Mesh Terms:
Acetyltransferases, Active Transport, Cell Nucleus, Animals, Anoxia, Cell Cycle Proteins, Glucose Transporter Type 1, Histone Acetyltransferases, Histone Deacetylases, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Monosaccharide Transport Proteins, Protein Binding, Rats, Repressor Proteins, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Up-Regulation, Vascular Endothelial Growth Factor A, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Oct. 01, 2004
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