TY - JOUR
T1 - Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression
AU - Sato, Fuyuki
AU - Bhawal, Ujjal Kumar
AU - Kawamoto, Takeshi
AU - Fujimoto, Katsumi
AU - Imaizumi, Tadaatsu
AU - Imanaka, Tadanobu
AU - Kondo, Jun
AU - Koyanagi, Satoru
AU - Noshiro, Mitsuhide
AU - Yoshida, Hidemi
AU - Kusumi, Tomomi
AU - Kato, Yukio
AU - Kijima, Hiroshi
PY - 2008/2
Y1 - 2008/2
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=38849110894&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38849110894&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2443.2007.01153.x
DO - 10.1111/j.1365-2443.2007.01153.x
M3 - Article
C2 - 18233956
AN - SCOPUS:38849110894
VL - 13
SP - 131
EP - 144
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 2
ER -