Identification of regulatory factors for somatic imprinted DMR establishment and elucidation of their molecular mechanisms
Project/Area Number |
17K08687
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Human genetics
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Research Institution | Saga University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 体細胞性インプリントDMR / DNAメチル化 / ゲノムインプリンティング / メチル化可変領域 / 遺伝子発現 / エピジェネティクス |
Outline of Final Research Achievements |
We screened regulatory factors for somatic imprinted DMR establishment within Igf2r/Airn domain using shRNA libraries. We found six genes as candidates. Second-order analyses revealed two genes as putative regulatory factors for the somatic DMR establishment. In addition, we generated model mice, in which candidate regions for DMR establishment were deleted, to clarify a mechanism of DMR establishment within Kcnq1ot1/Cdkn1c domain. Since DMR methylation did not change in the model mice, it was suggested that the regulatory region for DMR establishment did not exist within the deleted region. However, it was suggested that at least the enhancer for Cdkn1c would be included within the deleted region because Cdkn1c expression decreased in the model mice.
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Academic Significance and Societal Importance of the Research Achievements |
インプリント関連疾患では、配偶子形成過程で確立されるgDMRだけではなく、着床後に確立されるsDMRのメチル化も重要である。sDMRのメチル化を制御する因子の同定を目的に、Igf2r/Airn領域を対象に解析したところ、候補制御因子を2種類同定した。一方、Kcnq1ot1/Cdkn1c領域では、少なくともCdkn1cの候補エンハンサーの存在を突き止めた。インプリンティングの分子機構解明と疾患の病態解明に寄与する結果と考えられる。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.2019
Author(s)
Watanabe H, Higashimoto K, Miyake N, Morita S, Horii T, Kimura M, Suzuki T, Maeda T, Hidaka H, Aoki S, Yatsuki H, Okamoto N, Uemura T, Hatada I, Matsumoto N, Soejima H.
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Journal Title
FASEB J.
Volume: 34
Issue: 1
Pages: 960-973
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Growing oocyte specific transcription-dependent de novo DNA methylation at the imprinted Zrsr1-DMR2018
Author(s)
Joh, K., Matsuhisa, F., Kitajima, S., Nishioka, K., Higashimoto, K., Yatsuki, H., Kono, T., Koseki, H., Soejima, H.
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Journal Title
Epigenetics & Chromatin
Volume: 11
Issue: 1
Pages: 28-28
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive methylation analysis of imprinting-associated differentially methylated regions in colorectal cancer.2018
Author(s)
Hidaka H, Higashimoto K, Aoki S, Mishima H, Hayashida C, Maeda T, Koga Y, Yatsuki H, Joh K, Noshiro H, Iwakiri R, Kawaguchi A, Yoshiura KI, Fujimoto K, Soejima H.
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Journal Title
Clin Epigenetics
Volume: 10
Issue: 1
Pages: 150-150
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The allele frequency of ALDH2*Glu504Lys and ADH1B*Arg47His for the Ryukyu islanders and their history of expansion among East Asians2017
Author(s)
Koganebuchi, K., Haneji, K., Toma, T., Joh, K., Soejima, H., Fujimoto, K., Ishida, H., Ogawa, M., Hanihara, T., Harada, S., Kawamura, S. and *Oota, H.
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Journal Title
American Journal of Human Biology
Volume: 29
Issue: 2
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome2017
Author(s)
Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
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Journal Title
Human Mutation
Volume: 印刷中
Issue: 6
Pages: 637-648
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] CTCF deletion syndrome: Clinical features and epigenetic delineation2017
Author(s)
Hori I, Kawamura R, Nakabayashi K, Watanabe H, Higashimoto K, Tomikawa J, Ieda D, Ohashi K, Negishi Y, Hattori A, Sugio Y, Wakui K, Hata K, Soejima H, Kurosawa K, Saitoh S
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Journal Title
Journal of Medical Genetics
Volume: 54
Issue: 12
Pages: 836-842
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] IGF2 overexpression due to IGF2-DMR0 hypomethylation in Sotos syndrome.2019
Author(s)
Higashimoto K, Watanabe H, Miyake N, Morita S, Horii T, Maeda T, Hidaka H, Aoki S, Yatsuki H, Okamoto N, Hatada I, Matsumoto N, Soejima H.
Organizer
The 59th Annual Meeting of The Japanese Teratology Society, The 13th World Congress of The International Cleft Lip and Palate Foundation
Related Report
Int'l Joint Research / Invited
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[Presentation] Germline mutations associated with polycomb repressive complex 2 cause Weaver syndrome2017
Author(s)
Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N, Matsunaga S, Ryo A, Sato Y, Sanefuji M, Ihara K, Takada Y, Nishimura G, Saitsu H, Mizuguchi T, Miyatake S, Nakashima M, Miyake N, Soejima H, Matsumoto N
Organizer
The 67th Annual Meeting of the American Society of Human Genetics
Related Report
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