2007 Fiscal Year Final Research Report Summary
Mechanisms underlying the role of DNA methylation in fetal programming of adult disease in the neonatal mouse
| Project/Area Number |
18591224
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Tohoku University (2007)
Iwate Medical University (2006) |
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Principal Investigator |
MUROTSUKI Jun Tohoku University, Tohoku University Hospital, Associate Professor (50239555)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Yoshihiko Graduate School of Medicine, 環境医学研究所, Associate Professor (70250933)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Developmental origin of health and disease / epigenetics / pregnant mouse / fetus / Oct-4 / SPHK-1 / protein restriction / microarray |
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| Research Abstract |
The developmental origins hypothesis postulates that during critical ontogenetic periods, transient environmental stimuli perturb developmental pathways and induce permanent changes in gene expression, metabolism, and chronic disease susceptibility. One likely mechanism is via early nutritional influences on epigenetic gene modification consisting of the presence of a methyl group on the carbon 5 of a cytosine residue. This modification is responsible for an important form of gene regulation in eukaryotes. In the present study, we have tested the hypothesis that maternal low-protein diet altered epigenetic regulation of specific gene of the offspring. C57BL/6 female mice were mated and on the day the plug was detected, these females were then randomly allocated to be fed isocaloric diets consisting 18% protein or 9% protein. At delivery, offspring were kissed and the livers were removed immediately, frozen in liquid nitrogen and stored at -80C. Genomic sequencing after bisulfite modification is used to study site-specific DNA methylation. DNA methylation status of Oct-4 and Sphk-1 gene upstream regions in the mouse liver was analyzed. Hepatic Oct-4 or Sphk-1 promoter methylation was not significantly different between both groups. However, DNA methylation pattern of the genomic DNA is specific in low-protein diet group, Aberrant Oct-4 and Sphk-1 gene expression may cause perturbations in cell differentiation. We suggest that the epigenetic mechanism consisting of DNA methylation underlies the fetal programming theory.
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