Identification of a PDGF-responsive element in the murine c-myc gene.
The c-myc gene is rapidly induced in quiescent Balb/c-3T3 cells in response to the platelet-derived growth factor (PDGF). In order to study the mechanisms by which growth factors regulate induction of c-myc, we have attempted to identify growth factor-responsive elements in the murine c-myc locus. Various fragments of the c-myc gene linked to a bacterial CAT reporter gene were stably transfected into Balb/c-3T3 cells. A construct which includes the P1 promoter and 424 bp of upstream sequences shows a 3-5 fold induction of CAT RNA expression in response to sis/PDGF. S1 nuclease mapping experiments demonstrate that this mRNA initiates from the myc P1 promoter. Nuclear runoff transcription experiments performed with this myc/CAT construct show that this induction occurs at the transcriptional level. Deletion analysis led to the identification of an 81 bp segment in the first exon between the c-myc P1 and P2 promoters which is necessary to confer growth factor responsiveness in this construct.
Sacca
R
R
Massachusetts Institute of Technology, Center for Cancer Research, Cambridge 02139.
Cochran
B H
BH
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002872:Chromosome Deletion; D016259:Genes, myc / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015183:Restriction Mapping; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D010982:Platelet-Derived Growth Factor; D015500:Chloramphenicol O-Acetyltransferase; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate