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

✍ Scribed by Alia Al-Sarraj; Regina M. Day; Gerald Thiel

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 246 KB
• Volume: 94
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20305

✦ Synopsis

Abstract

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. © 2004 Wiley‐Liss, Inc.