title: Promoter-binding and repression of PDGFRB by c-Myc are separable activities.
abstract: 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.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Daniel Y L
authors.initials: DY
authors.lastname: Mao
authors.forename: Dalia
authors.initials: D
authors.lastname: Barsyte-Lovejoy
authors.forename: Cynthia S W
authors.initials: CS
authors.lastname: Ho
authors.forename: John D
authors.initials: JD
authors.lastname: Watson
authors.forename: Angelina
authors.initials: A
authors.lastname: Stojanova
authors.forename: Linda Z
authors.initials: LZ
authors.lastname: Penn
mesh_terms: 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
chemical_list: 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