Study on role of the placenta-specific gene to imprint in the nuclear initialization

• Project/Area Number: 26870036
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology; Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: Chiba Hatune 東北大学, 医学系研究科, 助教 (80642719)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ゲノムインプリンティング / メチル化インプリント / クローンマウス / 胎盤 / 胎盤形成 / DNAメチル化 / ヒストン修飾 / 遺伝子 / ゲノム / 発生・分化

Outline of Final Research Achievements

Both Gab1 and Sfmbt2 are novel placenta-specific imprinted genes and we analyzed the function and regulatory mechanism of Gab1 and Sfmbt2 using Gab1 KO mice, trophoblast stem cells and cloned mice. We found that the paternal expression of Gab1 and Sfmbt2 were 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 and Sfmbt2 DMR were lost and Gab1 and Sfmbt2 were highly expressed, which may contribute to placentomegaly of cloned mice.

Research Products

• [Journal Article] Genome-Scale Assessment of Age-Related DNA Methylation Changes in Mouse Spermatozoa. (2016)
  • Author(s): Kobayashi N, Okae H, Hiura H, Chiba H, Shirakata Y, Hara K, Tanemura K, Arima T.
  • Journal Title: PLoS One. Volume: 11
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allele-specific methylome and transcriptome analysis reveals widespread imprinting in the human placenta. (2016)
  • Author(s): Hamada H, Okae H, Toh H, Chiba H, Hiura H, Shirane K, Sato T, Suyama M, Yaegashi N, Sasaki H & Arima T.
  • Journal Title: The American Journal of Human Genetics Volume: 99 Pages: 1-11
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DNA methylation errors in imprinting disorders and male infertility. (2015)
  • Author(s): Kitamura A, Hiura H, Miyauchi N, Okae H, Chiba H, Arima T.
  • Journal Title: Congenit Anom (Kyoto) Volume: 55 Pages: 133-144
• [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
• [Presentation] ヒト凍結融解胚移植胎盤におけるmicroRNAの網羅的解析 (2016)
  • Author(s): 樋浦仁、服部裕充、岡江寛明、千葉初音、宮内尚子、北村茜、菊地裕幸、吉田秋仁、有馬隆博
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] 繁殖期におけるマウス精子DNAメチル化様式の加齢性変化 (2016)
  • Author(s): 小林記緒、岡江寛明、樋浦仁、千葉初音、白形芳樹、原健士郎、種村健太郎、有馬隆博
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] ヒト胚発生におけるエピジェネティクスの変調 (2015)
  • Author(s): 有馬隆博、樋浦仁、岡江寛明、千葉初音、宮内尚子
  • Organizer: 第33回受精着床学会
  • Place of Presentation: TFTホール（東京都江東区）
  • Year and Date: 2015-11-26
  • Invited
• [Book] Pharma Medica (2016)
  • Author(s): 有馬隆博、宮内尚子、北村茜、樋浦仁、岡江寛明、千葉初音
  • Total Pages: 144
  • Publisher: メディカルレビュー社
• [Book] 医学のあゆみ (2014)
  • Author(s): 千葉初音、有馬隆博
  • Total Pages: 5
  • Publisher: 医歯薬出版株式会社