2005 Fiscal Year Final Research Report Summary
DNA Methylation Analyses in Pathology
| Project/Area Number |
15208027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHIOTANI Kunio The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (80196352)
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| Co-Investigator(Kenkyū-buntansha) |
DOI Kunio The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (70155612)
NAKAYAMA Hiroyuki The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (40155891)
TAKAHASHI Shinichiro The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00197146)
TANAKA Satoshi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (90242164)
UETSUKA Koji The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助手 (60251419)
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| Project Period (FY) |
2003 – 2005
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| Keywords | DNA methylation / Epigenetics / Adipogenesis / ES cell / Dimethyl Sulfoxide / DNA methyltransferase |
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| Research Abstract |
In mammalian genome, there are substantial number of T-DMRs that are differentially methylated depending on type or differentiation status of the cells. Combination of methylation/unmethylation of T-DMRs forms "DNA methylation profile" of the cell. In this study, we aimed to reveal correlation between disturbance of the DNA methylation profile and pathological changes caused by, for example, cytotoxic reagents. By comparing DNA methylation profiles of preadipocyte cells before and after the induction of differentiation, we found multiple differentiation status-dependent T-DMRs. Some of them indicated transient change in their methylation statuses, implying that the cell differentiation involves dynamic and flexible epigenetic changes. We also analyzed an effect of Dimethyl Sulfoxide (DMSO) on DNA methylation status of the embryoid bodies derived from a suspension culture of mouse ES cells. DMSO not only upregulated the expression of one of the DNA methyltransferases, Dnmt3a, but also caused both hyper-and hypo-methylation of some genomic regions. As for Dnmt3a, its relation to the occurrence, of cancer is suggested. Given that such a widely-used reagent disturbed epigenetic systems, it was proposed that the analyses of epigenetic abnormality should be conducted when toxicity of the chemicals is evaluated. Moreover, we identified an aberrantly methylated locus in the placental genome of cloned mouse conceptuses, which show a hyperplasia of certain layers of the placenta. This provided an example of potential link between disturbance of DNA methylation and a pathological change. We also indicated that Dnmt3a and Dnmt3b, both of which have been considered as de novo methyltransferase, are required for the maintenance of genomic DNA methylation in ES cells.
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