New paradigm of genomic imprinting at Gpr1/Zdbf2 locus

• Project/Area Number: 15H05579
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Genome biology
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: KOBAYASHI Hisato 東京農業大学, その他部局等, 准教授 (70632727)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000); Fiscal Year 2017: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: DNAメチル化 / エピゲノム / ゲノム刷り込み機構 / ゲノム刷り込み / エピジェネティクス / ＤＮＡメチル化 / 非コードRNA / ゲノム / 遺伝学 / 発生・分化 / 応用動物

Outline of Final Research Achievements

Parent-of-origin DNA methylation patterns at imprinted genes are established during gametogenesis and maintained after fertilization. However, we previously characterized the unusual regulation of the imprinted Zdbf2 locus, which requires an epigenetic switch during early embryogenesis. In this study, we revealed that this unique locus is not imprinted in marsupials without Zdbf2 long isoform switching DNA methylation mark. We also found that LTR retrotransposons　transcribed in oocytes drives specie-specific oocyte DNA methylomes and maternally-methylated potentially imprinted regions. These findings provide us with many hints to elucidate the complicated origin and mechanism of genome imprinting.

Academic Significance and Societal Importance of the Research Achievements

哺乳動物に存在するゲノム刷り込み機構は、両親由来のゲノムの機能的な補正をしながら胎児の発生を調整するしくみである。マウス・ヒト等の刷り込み機構の種間および発生比較解析により、真獣類あるいはヒト特有の刷り込み機構の成立と機序を明らかにすることができた。今後の生殖補助医療において、流産・奇形のリスクを下げるため、本研究で明らかにしたヒト特有の刷り込み情報を卵子評価に応用することが期待される。

Research Products

• [Int'l Joint Research] The University of British Columbia/Department of Medical Genetics/Molecular Epigenetics Group(カナダ)
• [Int'l Joint Research] The University of British Columbia/Department of Medical Genetics/Molecular Epigenetics Group(Canada)
• [Int'l Joint Research] The University of British Columbia/Department of Medical Genetics/Molecular Epigenetics Group(Canada)
• [Journal Article] Sex-specific histone modifications in mouse fetal and neonatal germ cells (2019)
  • Author(s): Kawabata Yukiko、Kamio Asuka、Jincho Yuko、Sakashita Akihiko、Takashima Tomoya、Kobayashi Hisato、Matsui Yasuhisa、Kono Tomohiro
  • Journal Title: Epigenomics Volume: 11 Issue: 5 Pages: 543-561
  • DOI: 10.2217/epi-2018-0193
  • Peer Reviewed / Open Access
• [Journal Article] LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation (2018)
  • Author(s): Brind’Amour Julie、Kobayashi Hisato、Richard Albert Julien、Shirane Kenjiro、Sakashita Akihiko、Kamio Asuka、Bogutz Aaron、Koike Tasuku、Karimi Mohammad M.、Lefebvre Louis、Kono Tomohiro、Lorincz Matthew C.
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 3331-3331
  • DOI: 10.1038/s41467-018-05841-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Repression of somatic genes by selective recruitment of HDAC3 by BLIMP1 is essential for mouse primordial germ cell fate determination (2018)
  • Author(s): Mochizuki Kentaro, Hayashi Yohei, Sekinaka Tamotsu, Otsuka Kei, Ito-Matsuoka Yumi, Kobayashi Misato, Oki Shinya, Takehara Asuka, Kono Tomohiro, Osumi Noriko, Matsui Yasuhisa
  • Journal Title: Cell Reports Volume: 24 Issue: 10 Pages: 2682-2693
  • DOI: 10.1016/j.celrep.2018.07.108
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between PIWIL4-mediated H3K4me2 demethylation and piRNA-dependent DNA methylation. (2018)
  • Author(s): Nagamori, I., Kobayashi, H., Nishimura, T., Yamagishi, R., Katahira, J., Kuramochi-Miyagawa, S., Kono, T., Nakano, T.
  • Journal Title: Cell Reports Volume: 25 Issue: 2 Pages: 350-356
  • DOI: 10.1016/j.celrep.2018.09.017
  • Peer Reviewed / Open Access
• [Journal Article] DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells (2018)
  • Author(s): Tatsumi Daiki、Hayashi Yohei、Endo Mai、Kobayashi Hisato、Yoshioka Takumi、Kiso Kohei、Kanno Shinichiro、Nakai Yuji、Maeda Ikuma、Mochizuki Kentaro、Tachibana Makoto、Koseki Haruhiko、Okuda Akihiko、Yasui Akira、Kono Tomohiro、Matsui Yasuhisa
  • Journal Title: PLOS ONE Volume: 13 Issue: 11 Pages: e0205969-e0205969
  • DOI: 10.1371/journal.pone.0205969
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling (2018)
  • Author(s): Mochizuki Kentaro, Tando Yukio, Sekinaka Tamotsu, Otsuka Kei, Hayashi Yohei, Kobayashi Misato, Kamio Asuka, Ito-Matsuoka Yumi, Takehara Asuka, Kono Tomohiro, Osumi Noriko, Matsui Yasuhisa
  • Journal Title: Development Volume: 145 Issue: 23 Pages: 1-10
  • DOI: 10.1242/dev.164160
  • Peer Reviewed
• [Journal Article] Inducible Transposition of a Heat-Activated Retrotransposon in Tissue Culture (2017)
  • Author(s): Masuta Y, Nozawa K, Takagi H, Yaegashi H, Tanaka K, Ito T, Saito H, Kobayashi H, Matsunaga W, Masuda S, Kato A, Ito H
  • Journal Title: Plant and Cell Physiology Volume: 58 Pages: 375-384
  • DOI: 10.1093/pcp/pcw202
  • NAID: 120006382279
  • Peer Reviewed
• [Journal Article] Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas (2017)
  • Author(s): Fukushima S, Yamashita S, Kobayashi H, et al.; Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium).
  • Journal Title: Acta Neuropathologica Volume: 133 Issue: 3 Pages: 445-462
  • DOI: 10.1007/s00401-017-1673-2
  • Peer Reviewed / Open Access
• [Journal Article] DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion (2016)
  • Author(s): Koike T, Wakai T, Jincho Y, Sakashita A, Kobayashi H, Mizutani E, Wakayama S, Miura F, Ito T, Kono T
  • Journal Title: Biol Reprod Volume: 94 Issue: 6 Pages: 1-7
  • DOI: 10.1095/biolreprod.116.138677
  • Peer Reviewed / Open Access
• [Journal Article] Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice (2016)
  • Author(s): Fukuda A, Mitani A, Miyashita T, Kobayashi H, Umezawa A, Akutsu H
  • Journal Title: Reproduction Volume: 152 Issue: 5 Pages: 417-30
  • DOI: 10.1530/rep-16-0277
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Repetitive DNA methylome analysis by small-scale and single-cell shotgun bisulfite sequencing. (2016)
  • Author(s): Kobayashi H, Koike T, Sakashita A, Tanaka K, Kumamoto S, Kono T
  • Journal Title: Genes Cells Volume: 21 Issue: 11 Pages: 1209-1222
  • DOI: 10.1111/gtc.12440
  • NAID: 130007024787
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal mouse testis. (2015)
  • Author(s): Kubo N, Toh H, Shirane K, Shirakawa T, Kobayashi H, Sato T, Sone H, Sato Y, Tomizawa S, Tsurusaki Y, Shibata H, Saitsu H, Suzuki Y, Matsumoto N, Suyama M, Kono T, Ohbo K, Sasaki H.
  • Journal Title: BMC Genomics. Volume: 16 Issue: 1 Pages: 624-624
  • DOI: 10.1186/s12864-015-1833-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive DNA Methylation Analysis of Retrotransposons in Male Germ Cells (2015)
  • Author(s): Nagamori I, Kobayashi H, Shiromoto Y, Nishimura T, Kuramochi-Miyagawa S, Kono T, Nakano T.
  • Journal Title: Cell Rep. Volume: 12 Issue: 10 Pages: 1541-1547
  • DOI: 10.1016/j.celrep.2015.07.060
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sunflower centromeres consist of a centromere-specific LINE and a chromosome-specific tandem repeat (2015)
  • Author(s): Nagaki K, Tanaka K, Yamaji N, Kobayashi H, Murata M
  • Journal Title: Frontiers in Plant Science Volume: 6 Pages: 12-12
  • DOI: 10.3389/fpls.2015.00912
  • Peer Reviewed / Open Access
• [Journal Article] Sex Specification and Heterogeneity of Primordial Germ Cells in Mice. (2015)
  • Author(s): Sakashita, A., Kawabata, Y., Jincho, Y., Tajima, S., Kumamoto, S., Kobayashi, H., Matsui, Y. and Kono, T.
  • Journal Title: PLoS ONE Volume: 10 Issue: 12 Pages: 1-21
  • DOI: 10.1371/journal.pone.0144836
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 内在性レトロトランスポゾンが哺乳動物卵子DNAメチロームの多様性を生み出す (2018)
  • Author(s): 小林久人、Brind’Amour J, Richard Albert J, 白根健次郎, 坂下陽彦, 神尾明日香, Karimi MM, Lefebvre L, 河野友宏, Lorincz MC
  • Organizer: 第12回エピジェネティクス研究会
• [Presentation] ヒト・ラット，マウス卵子のDNAメチローム比較解析 (2018)
  • Author(s): 小林久人、Brind’Amour J, Richard Albert J, 白根健次郎, 坂下陽彦, 神尾明日香, Karimi MM, Lefebvre L, 河野友宏, Lorincz MC
  • Organizer: 第111回日本繁殖生物学会大会
• [Presentation] マウスのゲノム包括的なアレル特異的DNAメチローム解析 (2017)
  • Author(s): 小林久人
  • Organizer: 第5回NGS現場の会
• [Presentation] DNA methylome analysis in mouse germ cells and early embryos (2016)
  • Author(s): 小林久人
  • Organizer: Genomic Imprinting, Epigenetics and Physiological Functions
  • Place of Presentation: エーリチェ・シチリア州、イタリア
  • Year and Date: 2016-10-02
  • Int'l Joint Research
• [Presentation] ゲノミックインプリンティング～全ゲノムバイサルファイトシーケンス解析から“目印”として働くDNAメチル化の本質を探る～ (2016)
  • Author(s): 小林久人
  • Organizer: 第５回生命医薬情報学連合大会
  • Place of Presentation: 東京国際交流館プラザ平成、東京都江東区、日本
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] 小規模およびシングルセルショットガンバイサルファイトシーケンス解析による生殖細胞系列における反復配列特性の解明 (2015)
  • Author(s): 小林久人、小池佐、坂下陽彦、田中啓介、河野友宏
  • Organizer: 第38回日本分子生物学会・BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 次世代シーケンサーを利用した新しい農学研究分野の開拓 (2015)
  • Author(s): 小林久人
  • Organizer: 日本動物遺伝育種学会第16回大会
  • Place of Presentation: 神戸大学
  • Year and Date: 2015-11-07
  • Invited
• [Presentation] 小規模およびシングルセルショットガンバイサルファイトシーケンス解析による生殖細胞系列における反復配列特性の解明 (2015)
  • Author(s): 小林久人、小池佐、坂下陽彦、田中啓介、河野友宏
  • Organizer: 第108回 日本繁殖生物学会大会
  • Place of Presentation: 宮崎大学
  • Year and Date: 2015-09-16