Promoter-binding and repression of PDGFRB by c-Myc are separable activities.
The c-Myc transcription factor represses the mRNA expression of the platelet-derived growth factor receptor beta gene (PDGFRB). Using chromatin immunoprecipitation, we show that c-Myc binds to the proximal promoter of the PDGFRB gene in proliferating rat fibroblasts. Interestingly, mutant c-Myc proteins that are unable to repress PDGFRB gene expression, c-Myc(dBR) and c-Myc(d106-143), are still able to bind to the promoter in vivo. Hence, promoter-binding and repression of PDGFRB by c-Myc are separable activities. We also show that Myc repression of PDGFRB is not dependent on previously described or known transactivator-binding regions, suggesting Myc may be recruited to the promoter by multiple or yet unidentified transcription factors. In the presence of intact promoter-binding by Myc, trichostatin A (TSA) can block Myc repression of PDGFRB in vivo, again demonstrating that promoter-binding and repression are separable. Taken together, we hypothesize that Myc repression of PDGFRB expression occurs by a multi-step mechanism in which repression is initiated after Myc is recruited to the promoter.
Mao
Daniel Y L
DY
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
Barsyte-Lovejoy
Dalia
D
Ho
Cynthia S W
CS
Watson
John D
JD
Stojanova
Angelina
A
Penn
Linda Z
LZ
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006877:Hydroxamic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D015534:Trans-Activators; C012589:trichostatin A; D020797:Receptor, Platelet-Derived Growth Factor beta; D012319:RNA Polymerase II