Nuclear respiratory factor-1 (NRF-1) regulated hypoxia-inducible factor-1α (HIF-1α) under hypoxia in HEK293T

IUBMB Life. 2016 Sep;68(9):748-55. doi: 10.1002/iub.1537. Epub 2016 Aug 5.

Abstract

Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of oxygen homeostasis. Under hypoxia, the active HIF1-α subunits are mainly regulated through increased protein stabilization. Little is known concerning HIF-1α transcriptional regulation. Nuclear respiratory factor 1 (NRF-1) is a DNA-binding transcription factor that regulates mitochondrial biogenesis. In this study, we showed that NRF-1was a repressor of HIF-1α. The cellular depletion of NRF-1 by siRNA targeting leads to increased HIF-1αtranscriptional activity. EMSA, ChIP and luciferase activity allowed the identification of two functional NRF-1 binding sites within HIF-1α promoter. This study therefore identifies NRF-1 as a novel regulator of HIF-1α. © 2016 IUBMB Life, 68(9):748-755, 2016.

Keywords: gene transcription regulation; hypoxia-inducible factor 1α; nuclear respiratory factor-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Cell Hypoxia / genetics
  • DNA-Binding Proteins / genetics
  • HEK293 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Nuclear Respiratory Factor 1 / antagonists & inhibitors
  • Nuclear Respiratory Factor 1 / genetics*
  • Oxygen / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Transcriptional Activation / genetics*

Substances

  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NRF1 protein, human
  • Nuclear Respiratory Factor 1
  • RNA, Small Interfering
  • Oxygen