2007 Fiscal Year Final Research Report Summary
Research on the regulation of vertebrates' genome DNA methylation
| Project/Area Number |
17370047
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Osaka University |
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Principal Investigator |
TAJIMA Shoji Osaka University, Intitute of Protein Research, Professor (50132931)
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| Co-Investigator(Kenkyū-buntansha) |
SUETAKE Isao Osaka University, Institute of Protein Research, Associate Professor (80304054)
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| Project Period (FY) |
2005 – 2007
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| Keywords | DNA methylation / DNA methvltransferase / nucleosome / hisotne / Dnmtl / Dnmt3a / Dnmt3b / Np95 |
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| Research Abstract |
Genome in higher eukaryotes suffers methylation modification. This methylation affects not the coding but the expression information. The methylation modification is catalyzed by three DNA methyltransferases (Dnmt) and one related factor Dnmt3L, which has no catalytic activity. In the research project, we aimed to elucidate the molecular mechanism of the Dnmt on the creation and the maintenance of DNA methylation patterns, and obtained the following results.
Dnmtl, which contributes to the maintenance of genome methylation patterns, processively methylates hemimethylated CpG on a double-stranded DNA. Unexpectedly, Dnmt1 frequently fails to methylate hemimethylated positions. The N-terminal portion of Dnmt1 forms independent domain structure, and possesses DNA binding activity that recognizes minor grove of DNA. We found Np95 as a new factor that is necessary for the maintenance of DNA methylation patterns in vivo. These properties help in understanding the mechanism of the maintenance of DNA methylation patterns.
De novo-type enzyme Dnmt3a hardly methylates nucleosome core region, but that Dnmt3b can significantly methylates. Dnmt3a efficiently methylates the naked linker region of nucleosomes, and the activity is inhibited by linker histone H1. Histone H1 may contribute to the regulation in creating DNA methylation patterns by Dnmt3a. In male primordial germ cells (PGC), in which global methylation occurs, Dnmt3a2, which is an isoform of Dnmt3a, and Dnmt3L are highly expressed. Dnmt3L is prerequisite for the global methylation. We found that Dnmt3a2 cannot show catalytic activity under physiological salt conditions, but restores the activity in the presence of Dnmt3L. It is suggested that this salt-dependent catalytic activity of Dnmt3a2 is the reason why the global methylation in PGC requires Dnmt3L. These properties of Dnmt3 help in understanding the creation of DNA methylation patterns.
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