Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression

Fuyuki Sato, Ujjal Kumar Bhawal, Takeshi Kawamoto, Katsumi Fujimoto, Tadaatsu Imaizumi, Tadanobu Imanaka, Jun Kondo, Satoru Koyanagi, Mitsuhide Noshiro, Hidemi Yoshida, Tomomi Kusumi, Yukio Kato, Hiroshi Kijima

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

DEC1 (BHLHB2/Sharp2/Stra13) and DEC2 (BHLHB3/Sharp1) are basic-helix-loop-helix (bHLH) transcription factors, involved in cellular differentiation, responses to hypoxia and circadian rhythms. We recently showed that the expression of DEC1 and DEC2 was up-regulated by hypoxia; however, the functions of these two factors under hypoxic conditions have not been elucidated in detail. It is well established that the expression of vascular endothelial growth factor (VEGF) is up-regulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1α (HIF-1α) and arylhydrocarbon receptor nuclear translocator 1 (ARNT1). In the present study, we showed that DEC2, but not DEC1, suppressed VEGF gene expression under hypoxic conditions. DEC2 protein was co-immunoprecipitated with HIF-1α but not with ARNT1. The binding of HIF-1α to the hypoxia response element (HRE) in the VEGF promoter was decreased by DEC2 over-expression, and increased by DEC2 knockdown. We also showed that the circadian expression of VEGF showed a reciprocal pattern to that of DEC2 in cartilage. DEC2 had a circadian oscillation in implanted Sarcoma 180 cells. We conclude that DEC2 negatively regulates VEGF expression and plays an important role in the pathological conditions in which VEGF is involved. Journal compilation

Original languageEnglish
Pages (from-to)131-144
Number of pages14
JournalGenes to Cells
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 2008

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression'. Together they form a unique fingerprint.

Cite this