| Project/Area Number |
12671596
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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 |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
TAKEMURA Masahiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (50294062)
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| Co-Investigator(Kenkyū-buntansha) |
ISAKA Shigeyuki Osaka University, Graduate School of Medicine, Medical Staff, 医学部・附属病院, 医員
AZUMA Chihiro Osaka University, Graduate School of Medicine, Associate Professor, 医学部・附属病院, 助教授 (20151061)
KOYAMA Masayasu Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00183351)
信永 敏克 大阪大学, 医学系研究科, 講師 (40273677)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | oxytocin receptor / preterm labor / methylated DNA / uterine contraction / chorioamnionitis / transcription |
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| Research Abstract |
Chorioamnionitis is an important cause of preterm labor. We have revealed mechanisms of uterine contraction through investigations of oxytocin receptor. Expression of oxytocin receptor is known to increase significantly at labor. Mechanism of this oxytocin receptor induction at the time of labor was not revealed yet. We have been investigating the mechanism of transcriptional regulation of oxytocin receptor.
Methylation of cytosine residue in 5'-CpG-3' sequence is one of epigenetic modification processes of mammalian genome and is associated with transcriptional repression. Mammalian genome, contains CpG-rich stretches of 500-2000 base pairs in its regulatory region, which is called as CpG islands. Hypermethylation of this region leads to suppression of the gene. In human oxytocin receptor (OTR) gene, we revealed that the CpG islands existed from 140bp upstream to 2338 bp downstream of the transcription start site (TSS).
the present study, we investigated the relationship between DNA met
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hylation and expression level of OTR gene. HepG2 and Hep3B cells derived from human hepatoblastoma expressed only trace of OTR in back ground. OTR gene expression in these cells increased significantly by 5-azacytidine (Aza-C) treatment, which is a demethylating agent for nucleotide. However the OTR expression level in HELA and WISH cells, which are expressed OTR continuously, were not changed by demethylation of DNA. We revealed that the expression level of OTR gene is regulated by DNA methylation. We analyzed further by using plasmids containing processed transcriptional region of OTR gene and a reporter gene. Deletion of a segment named MT2 in the transcriptional region showed biggest influence to the reporter gene expression. The methylation condition of this MT2 region was most different between liver and uterus. The methylation of OTR transcription regulation region in vivo was also investigated. The degree of methylation in uterine myometrium was diminished at labor compared to the first trimester. Our results revealed that the methylation is an important regulation mechanism of OTR gene expression. Less
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