Transcriptional regulation of a new variant of human platelet-derived growth factor receptor alpha transcript by E2F-1.
Platelet-derived growth factors (PDGFs) and their receptors play an important role in cell proliferation, angiogenesis, and differentiation during normal development, and have also been implicated in tumorigenesis. In this study, we identified a novel variant of human PDGF receptor alpha mRNA (type II), which contains the same open reading frame as the known PDGF receptor alpha mRNA (type I) but a different 5'-untranslated region (5'-UTR). The 5'-UTR of the type II transcript was identified as a 363-bp exon located in intron 1 at position +1,210 to +1,572 relative to the transcriptional initiation site of the type I transcript. This type II transcript was expressed in a subset of human cell lines, such as MG-63 and MNNG/HOS cells. Moreover, transcription of the type II, but not the type I, was regulated by E2F-1 through an E2F-1-responsive site located at position +1,086/+1,093 downstream of the transcriptional initiation site of the type I transcript. Furthermore, epigenetic modulation might be involved in the expression of the type II transcript. Our findings provide new insights into the regulatory mechanism of PDGF receptor alpha transcription in normal and tumor cells.
Minato
Yusuke
Y
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Tashiro
Etsu
E
Kanai
Mai
M
Nihei
Yoshiaki
Y
Kodama
Yuki
Y
Imoto
Masaya
M
D020121:5' Untranslated Regions; D020029:Base Pairing; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D007668:Kidney / Q000166:cytology; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D016366:Open Reading Frames; D012516:Osteosarcoma / Q000473:pathology; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D017931:DNA Primers; D050687:E2F1 Transcription Factor; D012333:RNA, Messenger; D008156:Luciferases; D020796:Receptor, Platelet-Derived Growth Factor alpha