2005 Fiscal Year Final Research Report Summary
A molecular base of epigenetic gene expression control in imprinted domain
| Project/Area Number |
16590263
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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 |
Human genetics
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| Research Institution | Saga University |
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Principal Investigator |
SOEJIMA Hidenobu Saga University, Faculty of Medicine, Research Associate, 医学部, 助手 (30304885)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHIMOTO Ken Saga University, Faculty of Medicine, Research Associate, 医学部, 助手 (30346887)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Genomic imprinting / DNA methylation / Histone methylation / Beckwith-Wiedemann syndrome / cancer / Wilms tumor |
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| Research Abstract |
Genetic imprinting is the mechanisms that lead to parent-specific differential expression of a subset of mammalian genes. Chromosomal region 11p15.5 is a well-known imprinted region. Imprinted genes in the region are regulated by an imprinting control region (ICR), where is epigenetically marked. The imprinting disruption of the region plays an important role in the pathogenesis of human disorders, such as Beckwith-Wiedemann syndrome (BWS) and cancer. We investigated the molecular mechanism of the imprinting and relevance to diseases.
1.Loss of DNA methylation at DMR-LIT1, an ICR of KIP2/LIT1 imprinted domain, was commonly associated with loss of histone H3K9 methylation in BWS patients. In cancer, an imprinted tumor suppressor KIP2 is regulated by DMR-LIT1, which is far from KIP2. Analyses of ES cells targeted Dnmt1 or G9a indicated that methylations of DNA and H3K9 are important for the maintenance of imprinting.
2.We have tried to isolate candidate for imprinting control molecules by screening with protein-chip (SELDI-TOF MS) between normal and BWS cells. However, any molecule has not yet been identified.
3.Only mono-methylation at H4K20 among all methylations at lysine residues of H3 and H4 was specifically present at paternal DMR-Lit1, suggesting a novel imprinting mark.
4.From a comprehensive analysis of thirty-seven sporadic Wilms tumors, genetic or epigenetic abnormality of 11p was critical for Wilms tumorigenesis.
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