Reactivation of imprinted genes in Prader-Willi syndrome.
| Project/Area Number |
12670719
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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 |
Pediatrics
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SAITOH Shinji Hokkaido Univ., School of Med., Inst., 医学部・附属病院, 助手 (00281824)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIEDA Kenji Hokkaido Univ., School of Med., Prof., 医学部, 教授 (60173407)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | imprinting / epigenetics / DNA methylation / histone acetylation / Prader-Willi syndrome / Angelman syndrome / Prader-Willi症候群 / ゲノム刷り込み現象 / DNAメチル化 / ヒストンアセチル化 / Proder-Willi症候群 |
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| Research Abstract |
Prader-Willi syndrome (PWS) is associated with silencing of several imprinted genes located in 15q11-q13. These genes are epigenetically silenced through genomic imprinting although the genes are present. We have demonstrated that SNURF-SNRPN, which is a key imprinted locus in 15q11-q13, could be reactivated by drug treatment using 5-azadeoxycytidine (5-aza-dC) that inhibits DNA methylation. This reactivation was associated with not only demetylation of the CpG island of SNURF-SNRPN, but also increased level of histone acetylation. These results indicated that DNA methylation and histone acetylation played the critical roles in silencing of the imprinted genes.
We further investigated the possible reactivation of the homologous imprinted genes in mice. We used the fibroblasts established from the PWS mice models as well as control mice. Reactivation of Snurf-Snrpn in mice by 5-azadC was not as strong as in human. These preliminary results will help further investigation using mice models to test potential pharmaceutical treatment of imprinting related-disorders.
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Report
(3 results)
Research Products
(16 results)
