Bidirectional approach for elucidation of genomic imprinting mechanism
| Project/Area Number |
18590313
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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, Professor (30304885)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | genomic imprinting / KIP2 / LIT1 imprinted domain / Beckwith-Wiedemann syndrome / non-coding RNA / non-coding RNA / non-codin RNA |
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| Research Abstract |
Genomic imprinting is an epigenetic phenomenon that is responsible for parent-of-origin specific expression of genes. A disruption of imprinting at 11p 15.5 develops Beckwith-Wiedemann syndrome (BWS) and tumors. To clarify a molecular mechanism of genomic imprinting, we studied following issues.
1. Analysis of Japanese cases of BWS revealed a significantly lower frequency of H19-DMR hypermethylation and a higher frequency of chromosome abnormality than in North American and European patients. These results suggest that susceptibility to epigenetic and genetic alterations differs between the two groups.
2. Truncation cells in which short transcripts, 0.2 kb, 1.1 kb, and 6.6 kb, of LIT1were expressed were generated using a mouse hybrid cell containing human paternal chromosome 11. qRT-PCR revealed that expression of an imprinted KvLQT1 gene was drastically elevated in these cells. The result suggested that a non-coding transcript of LIT1 gene regulates expression of imprinted genes.
3. To identify a novel regulator for genomic imprinting, we tried to generate specific cells, which are able to be detected an imprinting disruption by neomycin-resistance. We constructed a knock-in vector in which IRES-neo cassette were inserted into downstream of an imprinted Kip2 gene. The vector was transfected into mouse ES cells ; however, no recombinant clone was obtained to date. Thus, we changed a construction of the vector, and we are now screening of ES cells. After obtained recombinant clones, we will generate Kip2-IRES-neo knock-in mice and establish mouse embryonic fibroblast.
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Report
(3 results)
Research Products
(52 results)
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[Journal Article] Japanese and North American/European patients with Beckwith-Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations.2007
Author(s)
Sasaki, K, Soejima, H, Higashimoto, K, Yatsuki, H, Ohashi, H, Yakabe, S, Joh, K, Niikawa, N, Mukai, T
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Journal Title
Eur JHum Genet 15(12)
Pages: 1205-10
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Duplication of the paternal IGF2 allele in trisomy 11 and elevated expression levels of IGF2 mRNA in congenital mesoblastic nephroma of the cellular or mixed type2007
Author(s)
Watanabe, N, Haruta, M, Soejima, H, Fukushi, D, Yokomori, K, Nakadate, H, Okita, H, Hata, J, Fukuzawa, M, Kaneko, Y
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Journal Title
Genes, Chromosomes and Cancer 46(10)
Pages: 929-935
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of DNA methylation and histone H3 Lysine 27 methylation in tissue-specific imprinting of mouse Grb 10.2007
Author(s)
Yamasaki-Ishizaki, Y, Kayashima, T, Mapendano, CK, Soejima, H, Ohta, T, Masuzaki, H, Kinoshita, A, Urano, T, Yoshiura, KI, Matsumoto, N, Ishimaru, T, Mukai, T, Niikawa, N, Kishino, T
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Journal Title
Mol Cell Biol 27(2)
Pages: 732-742
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 11q : Comparison with chromosome 21q.2006
Author(s)
Yamada, Y, Shirakawa, T, Taylor, Td, Okamura, K, Soejima, H, Uchiyama, M., Iwasaka, T, Mukai, T, Muramoto, Ki, Sakaki, Y, Ito, T
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Journal Title
DNA Sequence 17(4)
Pages: 300-306
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of 11q loss, trisomy 12 and possible 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor.2006
Author(s)
Watanabe, N, Nakadate, H, Haruta, M, Sugawara, W, Sasaki, F, Tsunematsu, Y, Kikuta, A, Fukuzawa, M, Okita, H, Hata, Ji, Soejima, H, Kaneko, Y
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Journal Title
Gene Chromosome Cancer 45(6)
Pages: 592-601
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumors2006
Author(s)
Satoh, Y, Nakadate, H, Nakagawachi, T, Higashimoto, K, Joh, K, Masaki, Z, Uozumi, J, Kaneko, Y, Mukai, T, Soejima, H
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Journal Title
Brit J Cancer 95(4)
Pages: 541-547
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers.2006
Author(s)
Nakano, S, Murakami, K, Meguro, M, Soejima, H, Higashimoto, K, Urano, T, Kugoh, H, Mukai, T, Ikeguchi, M., Oshimura, M
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Journal Title
Cancer Science 97(11)
Pages: 1147-1154
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 4 Imprinting related diseases, Chapter 5 Epigenetics and diseases, Genome Wide Development of Epigenetic Medical Science.(in Japanese)2006
Author(s)
Soejima, H, Ohta, T, Mukai, T
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Journal Title
(M, Nakao, K, Shiota, T, Ushijima, Sasaki H ed.)(Yodo-sha, Tokyo, Experimental Medicine) 24(8)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] SNP array analysis and H19-DMR CTCF6 methylation analysis revealed genetic and clinical heterogeneity of Wilms tumors with WT1 aberration2007
Author(s)
Kaneko, Y., Haruta, M., Arai, Y., Soejima, H., Watanabe, N., Fukuzawa, M
Organizer
The 52nd Annual Meeting of the Japanese Society of Human Genetics
Place of Presentation
Tokyo
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] A case with partial trisomy of 11p15 transmitted from mother2007
Author(s)
Shimokawa, O., Fu, R., Soejima, H., Sasaki, K., Kondo, T., Matsumoto, N., Yoshiura, K., Niikawa, N., Harada, N
Organizer
The 52nd Annual Meeting of the Japanese Society of Human Genetics
Place of Presentation
Tokyo
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] What molecular mechanism contributes to the different incidence rates between Japanese and Caucasian Wilms tumors?2007
Author(s)
Haruta, M., Watanabe, N., Nakadate, N., Fukuzwa, M., Soejima, H., Kaneko, Y
Organizer
66th Annual Meeting of the Japanese Cancer Association
Place of Presentation
Yokohama
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Different incidence of epigenetic and genetic alterations between Japanese and Caucasian patients with Beckwith-Wiedemann syndrome.2006
Author(s)
Soejima, H, Sasaki, K, Higashimoto, K, Joh, K, Niikawa N, Mukai, T
Organizer
11th International Congress of Human Genetics
Place of Presentation
Brisbane, Australia
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Loss of imprinting(LOI) of IGF2 and structural aberration of WT1 in Wilms tumors2006
Author(s)
Haruta, M, Nakadate, N, Watanabe, N, Fukuzawa, M, Soejima, H, Kaneko, Y
Organizer
65th Annual Meeting of the Japanese Cancer Association
Place of Presentation
Yokohama
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Expression of imprinted LI1/KCNQlOTl gene and Epigenetics of KvDMR12006
Author(s)
Nakano, S, Murakami, K, Meguro, M., Soejima, H., Higashimoto, K., Urano, T., Kugoh, H., Mukai, T., Ikeguchi, M., Oshimura, M
Organizer
The 51st Annual Meeting of the Japanese Society of Human Genetics
Place of Presentation
Yonago
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Different incidence of some epigenetic and genetic alterations between Japanese and Caucasian patients with Beckwith- Wiedemann syndrome2006
Author(s)
Soejima, H., Sasaki, K., Higashimoto, K., Yatsuki, H., Joh, K., Niikawa, N., Mukai, T
Organizer
International Genomic Imprinting Workshop 2006
Place of Presentation
Tokyo, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] U2afl-rsl/Murr1 loci are newly imprinted loci formed in mouse after the divergence between human and mouse.2006
Author(s)
Joh, K., Wang, Y., Zhang, Z., Yatsuki, H., Soejima, H., Mukai, T
Organizer
International Genomic Imprinting Workshop 2006
Place of Presentation
Tokyo, Japan
Description
「研究成果報告書概要(欧文)」より
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