E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence.
Previous experiments have demonstrated that transcription of the human c-fos oncogene is activated through the action of the 289-amino acid adenovirus E1A gene product. In this study we have utilized a series of c-fos promoter deletion and substitution mutants to define regulatory sequences that allow the induction by E1A. Although the deletion of upstream promoter sequences has varying degrees of effect on overall promoter activity, these deletions retain inducibility by E1A. This includes the deletion of the serum response element and two elements that bind the ATF transcription factor. In fact, a c-fos promoter deleted to position -53, which leaves the TATA element but no other known functional element, retains inducibility, indicating a role for the TATA element in E1A control. Indeed, substitution of the c-fos TATA element (TATAA) with a TATA sequence from the simian virus 40 early promoter (TATTTAT) abolishes E1A inducibility; this promoter does retain responsiveness to cAMP induction, however, demonstrating that this TATTTAT substitution is functional. We conclude that the E1A-dependent activation of c-fos transcription is mediated through an effect on a TATA-binding protein that has specificity for the TATAA sequence.
Simon
M C
MC
Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021.
Rooney
R J
RJ
Fisch
T M
TM
Heintz
N
N
Nevins
J R
JR
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014709:Vero Cells
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases