Specificity of transcriptional regulation by the zinc finger transcription factors Sp1, Sp3, and Egr-1

被引:61
作者
Al-Sarraj, A
Day, RM
Thiel, G
机构
[1] Univ Saarland, Ctr Med, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany
[2] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA
关键词
Sp1; Sp3; Egr-1; p21(WAF1/Cip1); angiotensin-converting enzyme;
D O I
10.1002/jcb.20305
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcription factors Sp1, Sp3, and Egr-1 bind with their zinc finger DNA-binding domains to GC-rich sequences in the regulatory regions of their target genes. The similarity of the DNA-binding sites of Sp1, Sp3, and Egr-1 has triggered the hypothesis that they compete for the same DNA-binding site. We have investigated the specificity of transcriptional regulation by Sp1, Sp3, and Egr-1 using dominant-negative mutants that block the DNA-binding site of Sp1, Sp3, or Egr-1 respectively. The results show that constitutive transcription of Sp1 regulated reporter genes, containing Sp1 sites derived from the aldolase C and p21(WAF1/Cip1) genes, or the long terminal repeat of HIV-1, was impaired by dominant-negative mutants of Sp1 and Sp3, but not by a dominant-negative Egr-1. Transcription mediated by Egr-1 was induced by transfection of expression vectors encoding wild-type or mutated Egr-1 or by stimulation of the extracellular signal-regulated protein kinase pathway via an inducible B-Raf-estrogen receptor fusion protein. In all cases transcription of Egr-1-regulated reporter genes, containing Egr-1 binding sites derived from the Egr-1 or the synapsin I gene was impaired by a dominant-negative Egr-1, but not by dominant-negative Sp1 or Sp3 mutants. These results show that there are genuine Sp1/Sp3 or Egr-1 controlled genes showing no cross-regulation of Sp1/Sp3 and Egr-1 through the same DNA-binding site. This does not exclude the existence of composite Sp1/Sp3/Egr-1 binding sites, where competition for a common DNA-binding site occurs. (C) 2004 Wiley-Liss, Inc.
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页码:153 / 167
页数:15
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