1999 Fiscal Year Final Research Report Summary
Target genes of RORα which controls postnatal development of cerebeller Purkinje cells
| Project/Area Number |
09680777
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH |
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Principal Investigator |
MATSUI Takashi University of Occupational and Environmental Health School of Medicine, Department of Molecular Biology Associate, 医学部, 助教授 (10140906)
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| Project Period (FY) |
1997 – 1999
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| Keywords | RORα / nuclear receptor / transcription regulation / Purkinje cells / promoter |
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| Research Abstract |
We analyzed regulatory mechanisms of transcription of three genes, Pcp-2, prosaposin and 5-lipoxygenase genes, which are expressed in the Purkinje cells and contain a RORα-responsive elemenet (RORE). RORα-dependent transcription of the Pcp-2 gene which does not contain a glucocorticoid responsive element was shown to be repressed by glucocorticoid receptor (GR). Reciprocally, GR-dependent transcription of MMTV promoter was repressed by RORα. Regions essential for the transcriptional antagonism was mapped to the N-terminus of GR and the C-terminus of RORα, respectively. Since RORα and GR did not directly interact each other, it was suggested that a novel mediator common for RORα and GR confers the transcriptional antagonism between them.
Prosaposin gene (pSAP) contains a RORE which is efficiently bound with RORα. Although RORα activated transcription of the tk gene promoter linked with the RORE of pSAP gene, it failed to activate transcription of pSAP gene both in P19 and HeLa cells. In contrast, although GRE linked to pSAP gene failed to activate its transcription in P19, it activated the transcription in HeLa cells. These results indicated that transcriptional activation by nuclear receptors is dependent both on type of promoter and cell-type. Since promoters of eukaryptic genes show a structural variety, basal transcriptional complex formed on the promoter might differ from one to another. Nuclear receptor bound with its cognate responsive element interact differently to the basal transcription complex.
Transcription of 5-lipoxygenase (5-LO) gene has been demonstrated to be repressed by RORα. We recently observed that the transcriptional repression results from suppression of EGR1 function which actc as a transactivator of this gene.
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