| First Author | Jin Y | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 25 | Pages | 22699-705 |
| PubMed ID | 21540178 | Mgi Jnum | J:174807 |
| Mgi Id | MGI:5141192 | Doi | 10.1074/jbc.M111.237024 |
| Citation | Jin Y, et al. (2011) RTEF-1, an upstream gene of hypoxia-inducible factor-1alpha, accelerates recovery from ischemia. J Biol Chem 286(25):22699-705 |
| abstractText | The amount of available hypoxia-inducible factor (HIF)-1alpha has been considered to be largely a consequence of post-translational modification by multiple ubiquitin-proteasome pathways. However, the role of transcriptional regulation of HIF-1alpha is less certain, and the mechanisms of transcriptional regulation of HIF-1alpha require further investigation. Here we report that related transcriptional enhancer factor-1 (RTEF-1), a member of the TEF transcriptional factor family, transcriptionally regulates the HIF-1alpha gene under normoxic and hypoxic conditions. The expression of HIF-1alpha mRNA was decreased in endothelial cells in which RTEF-1 was knocked down with siRNA. Sequential deletional analysis of the HIF-1alpha promoter revealed that the MCAT-like element in the HIF-1alpha promoter was essential for HIF-1alpha transcription. Binding of RTEF-1 to the MCAT-like element was confirmed by ChIP. Treatment of endothelial cells with a HIF-1 inhibitor resulted in retardation of RTEF-1-induced proliferation and tube formation. Moreover, increased HIF-1alpha expression was observed in transgenic mice expressing RTEF-1 under the VE-cadherin promoter (VE-Cad/RTEF-1). VE-Cad/RTEF-1 mice subjected to hindlimb ischemia demonstrated increased levels of HIF-1alpha, accelerated recovery of blood flow, and increased capillary density compared with littermate controls. These results identify RTEF-1 as a regulator of HIF-1alpha transcription, which results in up-regulation of HIF-1alpha and acceleration of recovery from ischemia. |
