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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
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E2F-1 directly regulates thrombospondin 1 expression.

Wei Ji1, Wei Zhang, Wuhan Xiao

  • 1Key Laboratory of Biodiversity and Conservation of Aquatic Organisms, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, People's Republic of China.

Plos One
|October 27, 2010
PubMed
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E2F-1 transcription factor activates Thrombospondin 1 (TSP1) gene expression. This finding reveals E2F-1 as a regulator of TSP1, impacting angiogenesis and potentially tumor growth.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Thrombospondin 1 (TSP1) inhibits angiogenesis, suppressing tumor growth and metastasis.
  • Understanding TSP1 regulators is crucial for elucidating its biological functions.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling TSP1 gene expression.
  • To identify upstream regulators of TSP1 and their role in angiogenesis.

Main Methods:

  • Promoter assays and Northern blot analysis to assess TSP1 transcription.
  • Site-directed mutagenesis of the TSP1 promoter to identify regulatory regions.
  • Quantitative real-time PCR and chromatin immunoprecipitation (ChIP) assays.
  • Western blot analysis to study the effect of pRB1.

Main Results:

  • E2F-1 activates TSP1 transcription via a specific responsive element (-144/-137) in the TSP1 promoter.
  • Knockdown of E2F-1 reduces TSP1 promoter activity, confirming in vivo relevance.
  • E2F-1 directly binds to the identified promoter region.
  • pRB1 dose-dependently suppresses E2F-1-induced TSP1 activation.

Conclusions:

  • TSP1 is a novel transcriptional target of E2F-1.
  • E2F-1 regulates angiogenesis by modulating TSP1 expression.