Functional analysis of a placenta-specific imprinted gene Gab1 in the placenta

• Project/Area Number: 24613001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: epigenetics
• Research Institution: Tohoku University
• Principal Investigator: OKAE Hiroaki 東北大学, 医学(系)研究科(研究院), 助教 (10582695)
• Co-Investigator(Kenkyū-buntansha): ARIMA Takahiro 東北大学, 大学院医学系研究科, 教授 (80253532)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゲノムインプリンティング / メチル化インプリント / 胎盤幹（TS）細胞 / ヒト胎盤幹（TS）細胞 / 胎盤幹 (TS) 細胞

Outline of Final Research Achievements

Gab1 is a novel placenta-specific imprinted gene and we analyzed the function and regulatory mechanism of Gab1 using Gab1 KO mice, trophoblast stem cells and cloned mice. We found that the paternal expression of Gab1 was regulated by a novel differentially methylated region (DMR) and the imprinted expression was important for normal placental development. We also found that in cloned mouse placentas, the Gab1 DMR was lost and Gab1 was highly expressed, which may contribute to placentomegaly of cloned mice.

Research Products

• [Journal Article] RNA sequencing-based identification of aberrant imprinting in cloned mice. (2014)
  • Author(s): Okae H, Matoba S, Nagashima T, Mizutani E, Inoue K, Ogonuki N, Chiba H, Funayama R, Tanaka S, Yaegashi N, Nakayama K, Sasaki H, Ogura A, Arima T.
  • Journal Title: Hum Mol Genet. Volume: 23 Pages: 992-1001
  • Peer Reviewed / Open Access
• [Journal Article] Imprinting methylation errors in ART. (2014)
  • Author(s): Hiura H, Okae H, Chiba H, Miyauchi N, Sato F, Sato A, Arima T.
  • Journal Title: Reproductive Medicine and Biology. Volume: 13 Pages: 193-202
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide analysis of DNA methylation dynamics during early human development (2014)
  • Author(s): Okae H, Chiba H, Hiura H, Hamada H, Sato A, Utsunomiya T, Kikuchi H, Yoshida H, Tanaka A, Suyama M, Arima T.
  • Journal Title: PLOS Genetics Volume: 10
  • Peer Reviewed / Open Access
• [Journal Article] Stability of the abnormal imprinting of human induced pluripotent stem cells (2013)
  • Author(s): Hiura H, Toyoda M, Okae H, Sakurai M, Miyauchi N, Sato A, Kiyokawa N, Okita H, Miyagawa Y, Akutsu H, Nishino K, Umezawa A, Arima T
  • Journal Title: BMC Genetics Volume: 14 Issue: 1 Pages: 32-32
  • DOI: 10.1186/1471-2156-14-32
  • Peer Reviewed
• [Journal Article] DNA methylation errors in imprinting disorders and assisted reproductive technologies. (2013)
  • Author(s): Chiba H, Hiura H, Okae H, Miyauchi N, Sato F, Sato A, Arima T.
  • Journal Title: Pediatrics international. Volume: 55 Issue: 5 Pages: 542-549
  • DOI: 10.1111/ped.12185
  • Peer Reviewed
• [Journal Article] Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression (2012)
  • Author(s): Hiroaki Okae, et al
  • Journal Title: Human Molecular Genetics Volume: 21 Issue: 3 Pages: 548-558
  • DOI: 10.1093/hmg/ddr488
  • Peer Reviewed
• [Journal Article] High-throughput detection of aberrant imprint methylation in the ovarian cancer by the bisulphite PCR-Luminex method. (2012)
  • Author(s): Hiura H, Okae H, Kobayashi H, Miyauchi N, Sato F, Sato A, Suzuki F, Nagase S, Sugawara J, Nakai K, Yaegashi N, Arima T.
  • Journal Title: BMC Medical Genomics Volume: 5 Issue: 1 Pages: 8-17
  • DOI: 10.1186/1755-8794-5-8
  • Peer Reviewed
• [Journal Article] Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproductive technologies. (2012)
  • Author(s): Hiura H, Okae H, Miyauchi N, Sato F, Sato A , Van De Pette M, John R M, Kagami M, Nakai K, Soejima H, Ogata T, Arima T.
  • Journal Title: Human Reproduction Volume: 27(8) Issue: 8 Pages: 2541-2548
  • DOI: 10.1093/humrep/des197
  • Peer Reviewed
• [Journal Article] 生殖補助医療由来の先天性ゲノムインプリンティング異常症 (2012)
  • Author(s): 有馬隆博、樋浦仁、岡江寛明
  • Journal Title: 日本生殖内分泌学会雑誌 Japanese Journal of Reproductive Endocrinology Volume: 17 Pages: 54-58
  • NAID: 40019434316
• [Presentation] Genome-wide analysis of DNA methylation dynamics during early human development (2014)
  • Author(s): Arima T. Okae H.
  • Organizer: International Human Epigenome Consortium (IHEC) Annual Meeting
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-10-06 – 2014-10-08
• [Presentation] Non-random loss of imprinting in cloned mice (2012)
  • Author(s): 岡江寛明、有馬隆博
  • Organizer: 第5回生殖系列の世代サイクルとエピゲノムネットワーク
  • Place of Presentation: 京都
• [Book] 臨床婦人科産科 (2014)
  • Author(s): 濱田裕貴、岡江寛明、有馬隆博
  • Total Pages: 8
  • Publisher: 医学書院
• [Book] 遺伝子医学MOOK25号 (2013)
  • Author(s): 千葉初音、岡江寛明、有馬隆博
  • Publisher: 株式会社メディカルドゥ
• [Book] 遺伝子医学MOOK 25号 (2013)
  • Author(s): 千葉初音、岡江寛明、有馬隆博
  • Publisher: 株式会社メディカルドゥ
• [Book] DNA METHYLATION (2012)
  • Author(s): Arima T, Okae H, Hiura H, Miyauchi N, Sato F, Sato A, Hayashi C.
  • Publisher: INTECH