2012 Fiscal Year Final Research Report
Biological significance of developmental gene silencing of Dnmt3b.
| Project/Area Number |
23651194
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical genome science
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| Research Institution | Osaka University |
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Principal Investigator |
AOTA Kiyoe (URA Kiyoe) 大阪大学, 医学系研究科, 准教授 (80289363)
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| Project Period (FY) |
2011 – 2012
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| Keywords | クロマチン / DNA メチル化 / Dnmt3b |
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| Research Abstract |
Methylation of cytosine C5 of CpG dinucleotides is a characteristic DNA modification in many eukaryotic genomes that plays an important role in developmental gene regulation. DNA methylation is mediated by Dnmt1, Dnmt3a, and Dnmt3b, however, it is not known how each Dnmt selects target CpG sites in the genome and control gene silencing during development. Since Dnmt3b expresses specifically in ES cells and undifferentiated hematopoietic cells and repressed differentiated cells, we hypothesized that “developmental silencing of Dnmt3 is important for normal organogenesis”. To address this issue, we established Dnmt3b -conditional transgenic mice Tg-loxDnmt3b using Cre/lox system. Over expression of Dnmt3b repress cell proliferation and differentiation in ex vivo culture of hematopoietic stem cells. Furthermore, Tg-loxDnmt3b, Nkx2-5/Cre double mutant mice exhibited growth retardation. These results show that abnormal expression of Dnmt accelerate out of control of developmental gene expression.
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