August 07, 2012 15:30 - 16:30
BSI Central Building 4F Seminar Room
Clarifying transcriptional regulation of genes is important to
understand their functions. In this study, the presenter analyzed
transcriptional regulatory mechanisms of the platelet-derived growth
factor receptor α (PDGFRα) gene.
The presenter found the up-regulation of PDGFRα at both protein and mRNA
levels in Cyclin D1-overexpressing NIH3T3 clones. Since Cyclin D1 leads
to activation of E2F-1 through phosphorylation of pRB, this result
raised the possibility of transcriptional regulation of the human PDGFRα
gene by E2F-1. The presenter found a region, whose transcriptional
activity was activated by E2F-1, approximately 1 kbp downstream of the
previously reported human PDGFRα gene promoter, whose activity was not
activated by E2F-1. A transcript transcribed from this region was
identified as a novel variant of human PDGFRα transcript (type II),
which contains the same open reading frame as the known PDGFRα
transcript (type I) but a different 5’-untranslated region (5’-UTR).
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
+1086/+1093 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.
However, the physiological roles of each transcript are still unclear.
If the mouse PDGFRα gene is regulated by a similar dual promoter system
to that for the human PDGFRα gene, a knockout mouse approach targeting
their 5’-UTRs would be one of the most valid tools to investigate the
physiological functions of PDGFRα transcripts. As a result, the type II
PDGFRα also existed in mice, and the expression of this transcript was
also regulated by E2F-1, as well as in humans.
In genes with polymorphisms in their 5’-UTRs attributed to multiple
promoters, alternative promoters are often responsible for tissue- or
developmental stage-specific expression. Indeed, different tissue
expression patterns between PDGFRα transcripts were observed.
Furthermore, the type II transcript was expressed predominantly in
embryos. Since PDGFRα has been reported to play crucial roles in normal
development; therefore, the type II PDGFRα transcript might be involved
in normal development.
- Open to Public
- Tadafumi Kato [Tadafumi Kato, Molecular Dynamics of Mental Disorders ]
Name: Tadafumi Kato