Transcription of the catalytic 180-kDa subunit gene of mouse DNA polymerase alpha is controlled by E2F, an Ets-related transcription factor, and Sp1

Biochim Biophys Acta. 2000 Jul 24;1492(2-3):341-52. doi: 10.1016/s0167-4781(00)00117-2.


We have isolated a genomic DNA fragment spanning the 5'-end of the gene encoding the catalytic subunit of mouse DNA polymerase alpha. The nucleotide sequence of the upstream region was G/C-rich and lacked a TATA box. Transient expression assays in cycling NIH 3T3 cells demonstrated that the GC box of 20 bp (at nucleotides -112/-93 with respect to the transcription initiation site) and the palindromic sequence of 14 bp (at nucleotides -71/-58) were essential for basal promoter activity. Electrophoretic mobility shift assays showed that Sp1 binds to the GC box. We also purified a protein capable of binding to the palindrome and identified it as GA-binding protein (GABP), an Ets- and Notch-related transcription factor. Transient expression assays in synchronized NIH 3T3 cells revealed that three variant E2F sites near the transcription initiation site (at nucleotides -23/-16, -1/+7 and +17/+29) had no basal promoter activity by themselves, but were essential for growth-dependent stimulation of the gene expression. These data indicate that E2F, GABP and Sp1 regulate the gene expression of this principal replication enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Carrier Proteins*
  • Catalysis
  • Cell Cycle / genetics
  • Cell Cycle Proteins*
  • DNA Polymerase I / genetics*
  • DNA Polymerase I / isolation & purification
  • DNA Polymerase I / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Gene Expression Regulation, Enzymologic*
  • Genes, Regulator
  • Humans
  • Mice
  • Molecular Sequence Data
  • Molecular Weight
  • Oncogene Proteins*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-ets
  • Retinoblastoma-Binding Protein 1
  • Sequence Homology, Nucleic Acid
  • Sp1 Transcription Factor / physiology*
  • Transcription Factor DP1
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic


  • Arid4a protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Elk3 protein, mouse
  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Retinoblastoma-Binding Protein 1
  • Sp1 Transcription Factor
  • Transcription Factor DP1
  • Transcription Factors
  • DNA Polymerase I