| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Paternally expressed genes 3 (Peg3) and 5 (Peg5), which were identified by our systematic screening of imprinted genes using a novel subtraction-hybridization method, are expressed in adult brain specifically. Peg3 encodes a large C2H2 type zinc finger protein, presumably functioning a novel DNA binding protein. Peg5 was idenfied with Neuronatin which was reported to be expressed firstly in rhombomere 3 and 5 at day 8.5 embryos and later in central nervus system. Using in situ hybridization technique, immuno-staining with specific antibodies, we demonstrated that Peg3 protein localized in nucleus of neuronal and glial cells in the adult brain. We also demonstrated that human PEG3 gene suppressed the tumorigenecity of glioma cells by introducing a complete PEG3 cDNA into the cells. These results suggested that PEG3 protein fuctions as a DNA binding protein and controls several genes functioning in cell cycles, and as a result acts as tumor suppressor in glial cells.
Systematic analysis of in situ hybridization of the imprinted genes we have isolated showed that the expression pattems in early embryos were divided to three groups, mesoderm specific, neural tissue specific and very low expression in the embryos. However, all imprinted genes so far analyzed showed high expression in the placental tissues including yolk sac. Because there existed a high correlation between high expression in the placental tissues and the imprinted status of the gene questioned, we proposed a novel hypothesis that imprinted genes are regulated to be expressed in the placenta, suggesting the biological significance of the genomic imprinting existed in the formation of placental tissues in mammals.
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