Platelet-derived growth factor receptor α gene is regulated by multiple first exons

Transcription of the platelet-derived growth factor receptor alpha (PDGFRA/Pdgfra) gene is considered to be precisely regulated. We have previously reported that the PDGFRA/Pdgfra gene is regulated by a dual promoter system in human and mouse, in which a novel PDGFRA/Pdgfra transcript has a first exon (exon 1 beta) different from that of the canonical PDGFRA/Pdgfra transcript (exon 1 alpha). To elucidate the function of each transcript, we first investigated the contribution of different PDGFRA transcripts to final protein levels. Notably, knockdown experiments suggested the existence of other PDGFRA transcripts, and we identified five additional first exons (exons 1 gamma, 1 delta, 1 epsilon, 1 zeta, and 1 eta) in intron 1 in both the human and mouse genes. The first exons of the mouse Pdgfra gene showed unique expression patterns: exon 1 alpha was broadly expressed; exon 1 beta was highly expressed in embryos; exon 1 gamma was observed at relatively high levels in the adult central nervous system (CNS); and exon 1 delta was expressed at relatively high levels in the developing CNS. Furthermore, in silico analysis of common putative transcription factor binding sites in the upstream regions of the first exons of both human and mouse PDGFRA/Pdgfra genes predicted common (such as Sry, Mzf1, and Cdx) and unique (such as Sox5, Lmo2, and GATA) transcription factors. Our findings show the diversity of the transcriptional regulation of the PDGFRA/Pdgfra gene. (C) 2019 Elsevier Inc. All rights reserved.