2014 Fiscal Year Final Research Report
Identification of a novel steroidogenic-enzyme and analysis of its transcriptional regulation through alternations of chromatin structure
| Project/Area Number |
24590347
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | GSTAファミリー / SF-1 / ステロイドホルモン / クロマチン |
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| Outline of Final Research Achievements |
Steroidogenic factor 1 (SF-1, also known as Ad4BP) plays a pivotal role in the regulation of expression of steroidogenesis-related genes. To identify novel SF-1-target genes, a genome-wide analysis was carried out. We found that human glutathione S-transferase A (GSTA) family genes (hGSTA1–4) are regulated by SF-1. All hGSTA genes were upregulated by transduction of SF-1 into hMSCs, while knockdown of endogenous SF-1 in H295R cells downregulated all hGSTA genes. ChIP and 3C assays revealed that the coordinated expression of the genes was based on changes in higher-order chromatin structure triggered by SF-1. In steroidogenesis, the gene products of hGSTA1 and hGSTA3 were shown to function in a coordinated fashion with 3β-HSD II. This result indicates that enzymes hGSTA1-1 and hGSTA3-3 could be considered new members of the group of SF-1 controlled steroidogenic enzymes and to participate in Δ5-Δ4 isomerization of steroid hormone precursors.
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| Free Research Field |
内分泌学
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