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

• Published in: Biochemical and biophysical research communications 2019-03, Vol.510 (4), p.489-494
• Main Authors: Minato, Yusuke, Kuwahara-Otani, Sachi, Maeda, Seishi, Yagi, Hideshi
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Exons; Gene Expression Regulation; Genomic structure; Humans; Mice; Multiple first exons; Multiple promoters; NIH 3T3 Cells; PDGFRα; Receptor, Platelet-Derived Growth Factor alpha - genetics; Transcription, Genetic; Transcriptional regulation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.01.029

Transcription of the platelet-derived growth factor receptor α (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 1β) different from that of the canonical PDGFRA/Pdgfra transcript (exon 1α). 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 1γ, 1δ, 1ε, 1ζ, and 1η) in intron 1 in both the human and mouse genes. The first exons of the mouse Pdgfra gene showed unique expression patterns: exon 1α was broadly expressed; exon 1β was highly expressed in embryos; exon 1γ was observed at relatively high levels in the adult central nervous system (CNS); and exon 1δ 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. •PDGFRA/Pdgfra gene is regulated by at least seven first exons in human and mouse.•Different first exons contribute to tissue-specific expression of mouse Pdgfra gene.•TF-binding site prediction improves understanding of PDGFRA/Pdgfra gene expression.