Regulation of gene expression reprogramming in the oocytes and embryos.

• Project Area: The germline: its developmental cycle and epigenome network
• Project/Area Number: 20062002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: AOKI Fugaku 東京大学, 大学院・新領域創成科学研究科, 教授 (20175160)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥63,500,000 (Direct Cost: ¥63,500,000); Fiscal Year 2012: ¥12,700,000 (Direct Cost: ¥12,700,000); Fiscal Year 2011: ¥12,700,000 (Direct Cost: ¥12,700,000); Fiscal Year 2010: ¥12,700,000 (Direct Cost: ¥12,700,000); Fiscal Year 2009: ¥12,700,000 (Direct Cost: ¥12,700,000); Fiscal Year 2008: ¥12,700,000 (Direct Cost: ¥12,700,000)
• Keywords: 卵 / 初期胚 / リプログラミング / エピジェネティクス / 受精 / 初期発生 / ヒストン変異体 / クロマチン / 遺伝子発現 / 全能性 / 着床前初期胚 / 新生血RNA

Research Abstract

To elucidate the mechanism regulating the reprogramming of gene expression after fertilization, I investigated the change in the gene expression pattern after fertilization in mice. I identified 4,000 genes which are expressed in the 1-cell stage embryos and found that in this set of genes, there are many genes which were not expressed before fertilization. The analysis for the dynamics of histone variants revealed that H2A and H3 variants are dramatically replaced in the whole genome just after fertilization, which would be involved in the regulation of gene expression reprogramming.

Research Products

• [Journal Article] The expression and nuclear deposition of histone H3.1 in murine oocytes and preimplantation embryos (2012)
  • Author(s): Kawamura M, Akiyama T, Tsukamoto S, Suzuki MG & Aoki F
  • Journal Title: J. Reprod. Dev Volume: 28 Pages: 557-562
  • NAID: 10031123300
  • URL: https://www.jstage.jst.go.jp/article/jrd/58/5/58_2012-074/_article
  • Peer Reviewed
• [Journal Article] The expression and nuclear deposition of histone H3.1 in murine oocytes and preimplantation embryos (2012)
  • Author(s): Kawamura M, Aoki F, 他3名
  • Journal Title: J. Reprod. Dev Volume: 58 Pages: 557-562
  • NAID: 10031123300
  • Peer Reviewed
• [Journal Article] Effect of RNAi-mediated knockdown of the Bombyx mori transformer-2 gene on the sex specific splicing of Bmdsx pre-mRNA. (2012)
  • Author(s): Suzuki MG, Aoki F, 他2名
  • Journal Title: Int. J. Dev. Biol. Volume: 56 Issue: 9 Pages: 693-699
  • DOI: 10.1387/ijdb.120049ms
  • Peer Reviewed
• [Journal Article] Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos (2011)
  • Author(s): Nashun B, Akiyama T, Suzuki MG & Aoki F
  • Journal Title: Epigenetics Volume: 6 Issue: 12 Pages: 1489-1497
  • DOI: 10.4161/epi.6.12.18206
  • Peer Reviewed
• [Journal Article] Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos (2011)
  • Author(s): Akiyama T, Suzuki O, Matsuda J & Aoki F
  • Journal Title: PLOS Genetics Volume: 7
  • Peer Reviewed
• [Journal Article] Involvement of murine nucleoplasmin 2 in the decondensation of sperm chromatin after fertilization (2011)
  • Author(s): Inoue A, Ogushi S, Saitou M, Suzuki MG & Aoki F
  • Journal Title: Biol. Reprod Volume: 85 Issue: 1 Pages: 70-77
  • DOI: 10.1095/biolreprod.110.089342
  • Peer Reviewed
• [Journal Article] Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos (2011)
  • Author(s): Akiyama T
  • Journal Title: PLOS Genetics Volume: 7 Issue: 10 Pages: e1002279-e1002279
  • DOI: 10.1371/journal.pgen.1002279
  • Peer Reviewed
• [Journal Article] Involvement of Murine Nucleoplasmin 2 in the Decondensation of Sperm Chromatin after Fertilization. (2011)
  • Author(s): Inoue, A
  • Journal Title: Biol.Reprod. Volume: 84(印刷中)(掲載確定)
  • Peer Reviewed
• [Journal Article] Changes in the nuclear deposition of histone H2A variants during preimplantation development in mice (2010)
  • Author(s): Nashun B, Yukawa M, Liu H, Akiyama T & Aoki F
  • Journal Title: Development Volume: 137 Issue: 22 Pages: 3785-3794
  • DOI: 10.1242/dev.051805
  • Peer Reviewed
• [Journal Article] Role of the nucleoplasmin 2 C-terminal domain in the formation of nucleolus-like bodies in mouse oocytes (2010)
  • Author(s): Inoue A & Aoki F
  • Journal Title: FASEB J Volume: 24 Issue: 2 Pages: 485-494
  • DOI: 10.1096/fj.09-143370
  • Peer Reviewed
• [Journal Article] Global gene silencing is caused by the dissociation of RNA polymerase II from DNA in mouse oocytes (2010)
  • Author(s): Abe K, Inoue A, Suzuki MG & Aoki F
  • Journal Title: J. Reprod. Dev Volume: 56 Pages: 502-507
  • NAID: 10027571758
  • URL: https://www.jstage.jst.go.jp/article/jrd/56/5/56_10-068A/_article
  • Peer Reviewed
• [Journal Article] Changes in the nuclear deposition of histone H2A variants during preimplantation development in mice (2010)
  • Author(s): Nashun, B., Yukawa, M.Liu, H., Akiyama, T., Aoki, F.
  • Journal Title: Development 137 Pages: 3785-3794
  • Peer Reviewed
• [Journal Article] Global gene silencing is caused by the dissociation of RNA polymerase II from DNA in mouse oocytes (2010)
  • Author(s): Abe, K., Inoue, A., Suzuki, M.G., Aoki F
  • Journal Title: J.Reprod.Dev 56 Pages: 502-507
  • NAID: 10027571758
  • Peer Reviewed
• [Journal Article] Role of the nucleoplasmin 2 C-terminal domain in the formation of nucleolus-like bodies in mouse oocytes (2010)
  • Author(s): Inoue, A., Aoki, F.
  • Journal Title: FASEB J. 24 Pages: 485-494
  • Peer Reviewed
• [Journal Article] Global gene silencing is caused by the dissociation of RNA polymerase II from DNA in mouse oocytes. (2010)
  • Author(s): Abe, K
  • Journal Title: J.Reprod.Dev. Volume: 56 Pages: 502-507
  • Peer Reviewed
• [Journal Article] Changes in the nuclear deposition of histone H2A variants during preimplantation development in mice. (2010)
  • Author(s): Nashun, B
  • Journal Title: Development Volume: 137 Pages: 3785-3794
  • Peer Reviewed
• [Journal Article] Role of the nucleoplasmin 2 C-terminal domain in the formation of nucleolus-like bodies in mouse oocytes (2010)
  • Author(s): Inoue, A
  • Journal Title: FASEB J 24 Pages: 485-494
  • Peer Reviewed
• [Journal Article] Expression of c-MYC in nuclear speckles during mouse oocyte growth and preimplantation development (2009)
  • Author(s): Suzuki T, Abe K, Inoue A, & and Aoki F
  • Journal Title: J. Reprod. Dev Volume: 55 Pages: 491-495
  • NAID: 10025616231
  • URL: https://www.jstage.jst.go.jp/article/jrd/55/5/55_09-069A/_article
  • Peer Reviewed
• [Journal Article] Expression of c-MYC in nuclear speckles during mouse oocyte growth and preimplantation development (2009)
  • Author(s): Suzuki, T., Abe, K., Inoue, A., Aoki, F.
  • Journal Title: J. Reprod.Dev. 55 Pages: 491-495
  • NAID: 10025616231
  • Peer Reviewed
• [Journal Article] Expression of c-MYC in nuclear speckles during mouse oocyte growth and preimplantation development (2009)
  • Author(s): Suzuki, T
  • Journal Title: J.Reprod.Dev. 55 Pages: 491-495
  • Peer Reviewed
• [Journal Article] Contribution of the oocyte nucleus and cytoplasm to the determination of meiotic and developmental competence in mice (2008)
  • Author(s): Inoue A, Nakajima R, Nagata M, & Aoki F
  • Journal Title: Hum. Reprod Volume: 23 Issue: 6 Pages: 1377-1384
  • DOI: 10.1093/humrep/den096
  • Peer Reviewed
• [Journal Article] Changes in H3K79 methylation during preimplantation development in mice (2008)
  • Author(s): Ooga M, Inoue A, Kageyama S, Akiyama T, Nagata M & Aoki F
  • Journal Title: Biol. Reprod Volume: 78 Pages: 413-424
  • URL: http://www.biolreprod.org/content/78/3/413.long
  • Peer Reviewed
• [Journal Article] Contribution of the oocyte nucleus and cytoplasm to the determination of meiotic and developmental competence in mice (2008)
  • Author(s): Inoue, A., Nakajima, R., Nagata, M. ,Aoki, F.
  • Journal Title: Hum. Reprod. 23 Pages: 1377-1384
  • Peer Reviewed
• [Journal Article] Roles of the first and second round of DNA replication in the regulation of zygotic gene activation in mice (2008)
  • Author(s): Sonehara, H., Nagata, M., Aoki, F.
  • Journal Title: J. Reprod.Dev 54 Pages: 381-384
  • NAID: 10024412492
  • Peer Reviewed
• [Journal Article] Changes in H3K79 methylation during preimplantation development in mice (2008)
  • Author(s): M., Inoue, A., Kageyama, S., Akiyama, I., Nagata, M., Aoki, F.
  • Journal Title: Biol.Reprod. 78 Pages: 413-424
  • Peer Reviewed
• [Journal Article] Roles of the first and second round of DNA replication in the regulation of zygotic gene activation in mice (2008)
  • Author(s): Sonehara H
  • Journal Title: J. Reprod. Dev 54 Pages: 381-384
  • Peer Reviewed
• [Journal Article] Contribution of the oocyte nucleus and cytoplasm to the determination of meiotic and developmental competence in mice (2008)
  • Author(s): Inoue A
  • Journal Title: Hum. Reprod 23 Pages: 1377-1384
  • Peer Reviewed
• [Journal Article] Changes in H3K79 methylation during preimplantation development in mice (2008)
  • Author(s): Ooga M
  • Journal Title: Biol. Reprod 78 Pages: 413-424
  • Peer Reviewed
• [Journal Article] Involvement of Murine Nucleoplasmin 2 in the Decondensation of Sperm Chromatin after Fertilization
  • Author(s): I Inoue, A., Ogushi, S., Saitou M., Suzuki, M.G., Aoki, F.
  • Journal Title: Biol.Reprod in press
  • Peer Reviewed
• [Presentation] マウス着床前初期胚におけるヒストンH2B ユビキチン化 (2013)
  • Author(s): 大我政敏、青木不学
  • Organizer: 第116回日本畜産学会
  • Place of Presentation: 広島
  • Year and Date: 2013-03-30
• [Presentation] Characterization of the gene expression in the 1-cell stage embryos (2012)
  • Author(s): Abe K, Yamamoto R, Oka G, Franke V, Vlahovicek K, Suzuki Y & Aoki F
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] Histone H2B ubiquitination in the mouse preimplantation embryos (2012)
  • Author(s): Ooga M & Aoki F
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] The profile of the genes transcribed at the onset of gene expression after fertilization (2012)
  • Author(s): Yamamoto R, Abe K, Franke V, Vlahovicek K, Suzuki Y & Aoki F
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] Characterization of the gene expression in the 1-cell stage embryos. (2012)
  • Author(s): 阿部健一郎、青木不学, 他5名
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] Histone H2B ubiquitination in the mouse preimplantation embryos. (2012)
  • Author(s): 大我正敏、青木不学
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] The profile of the genes transcribed at the onset of gene expression after fertilization. (2012)
  • Author(s): 山本竜馬、青木不学, 他4名
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-18
• [Presentation] マウスES細胞におけるヒストンH2AおよびH3変異体のゲノムワイド解析 (2012)
  • Author(s): 青木不学
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] マウスES細胞におけるヒストンH2AおよびH3変異体のゲノムワイド解析 (2012)
  • Author(s): 青木不学
  • Organizer: 日本生化学会
  • Place of Presentation: マリンメッセ福岡(福岡)(招待講演)
  • Year and Date: 2012-12-15
• [Presentation] Genome-scale profiling of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells. (2012)
  • Author(s): 青木不学
  • Organizer: The 24th Annual Meeting of the Korean Society for Molecular and Cellular Biology.
  • Place of Presentation: Seoul, Korea(招待講演)
  • Year and Date: 2012-10-12
• [Presentation] 受精前後におけるゲノムリプログラミングへのヒストン変異体置換の関与 (2012)
  • Author(s): 青木不学
  • Organizer: 日本畜産学会
  • Place of Presentation: 名古屋大学(名古屋市)(招待講演)
  • Year and Date: 2012-03-29
• [Presentation] マウス着床前初期胚におけるHistone H3 lysine 79メチル化の調節機構について (2012)
  • Author(s): 大我政敏、青木不学
  • Organizer: 第115回日本畜産学会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-03-28
• [Presentation] 発生過程におけるゲノムリモデリングへのH3変異体の関与について (2012)
  • Author(s): 河村真愛、秋山智彦、塚本智史、青木不学
  • Organizer: 第115回日本畜産学会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-03-28
• [Presentation] Genome-scale profiling of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells (2012)
  • Author(s): Aoki F
  • Organizer: The 24^<th> Annual Meeting of the Korean Society for Molecular and Cellular Biology
  • Place of Presentation: Seoul, Korea
• [Presentation] Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells (2011)
  • Author(s): Aoki F
  • Organizer: EMBO workshop, "Histone Variants & Genome Regulation"
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2011-10-14
• [Presentation] Genome-wide analysis of the chromatin composition of histone H2A and H3 variant in mouse embryonic stem cells (2011)
  • Author(s): 青木不学
  • Organizer: EMBO workshop, "Histone Variants & Genome Regulation"
  • Place of Presentation: Strasbourg(フランス)(招待講演)
  • Year and Date: 2011-10-14
• [Presentation] Genome wide analysis of the histone variant MacroH2A in mouse embryonic stem cell (2011)
  • Author(s): Yukawa M, Akiyama T, Aburatani, H, Abe, K & Aoki F
  • Organizer: EMBO workshop, "Histone Variants & Genome Regulation"
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2011-10-13
• [Presentation] The dynamics of H3.1 during oogenesis and pre-implantation development in mice (2011)
  • Author(s): Kawamura M, Akiyama T, Tsukamoto S & Aoki F
  • Organizer: EMBO workshop, "Histone Variants & Genome Regulation"
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2011-10-13
• [Presentation] Genome wide analysis of the histone variant MacroH2A in mouse embryonic stem cell (2011)
  • Author(s): 湯川将之
  • Organizer: BO workshop, "Histone Variants & Genome Regulation
  • Place of Presentation: Strasbourg(フランス)
  • Year and Date: 2011-10-13
• [Presentation] The dynamics of H3.1 during oogenesis and pre-implantation development in mice (2011)
  • Author(s): 河村真愛
  • Organizer: BO workshop, "Histone Variants & Genome Regulation
  • Place of Presentation: Strasbourg(フランス)
  • Year and Date: 2011-10-13
• [Presentation] 核移植胚におけるコアヒストン置換によるクロマチンの再構築 (2011)
  • Author(s): 秋山智彦、那順布和、青木不学
  • Organizer: 第52回 哺乳動物卵子学会
  • Place of Presentation: 那須塩原
  • Year and Date: 2011-05-21
• [Presentation] 核移植胚におけるコアヒストン置換によるクロマチンの再構築 (2011)
  • Author(s): 秋山智彦
  • Organizer: 哺乳動物卵子学会
  • Place of Presentation: 国際医療福祉大学(那須塩原)
  • Year and Date: 2011-05-21
• [Presentation] Involvement of histone variants replacement in the genome remodeling after fertilization (2010)
  • Author(s): Aoki F
  • Organizer: International Symposium on "Epigenome Network Development and Reprogramming of Germ Cells
  • Place of Presentation: Fukuoka
  • Year and Date: 2010-11-24
• [Presentation] Involvement of histone variants replacement in the genome remodeling after fertilization. (2010)
  • Author(s): Aoki, F
  • Organizer: International Symposium on "Epigenome Network Development and Reprogramming of Germ Cells
  • Place of Presentation: Fukuoka Kyushu University School of Medicine Centennial Hall
  • Year and Date: 2010-11-24
• [Presentation] The preferential incorporation of H2A.X into chromatin in early preimplantation embryos involves its C-terminal domain. (2010)
  • Author(s): Nashun B
  • Organizer: 69^<th> Annual Meeting of Society for Developmental Biology
  • Place of Presentation: Albuquerque, USA
  • Year and Date: 2010-08-09
• [Presentation] The preferential incorporation of H2A.X into chromatin in early preimplantation embryos involves its C-terminal domain (2010)
  • Author(s): Nashun B & Aoki F
  • Organizer: 69th Annual Meeting of Society for Developmental Biology
  • Place of Presentation: Albuquerque, USA
  • Year and Date: 2010-08-08
• [Presentation] Mechanism of global gene silencing and reactivation during oocyte growth at the one-cell stage after fertilization in mice (2010)
  • Author(s): Abe K
  • Organizer: 69^<th> Annual Meeting of Society for Developmental Biology
  • Place of Presentation: Albuquerque, USA
  • Year and Date: 2010-08-07
• [Presentation] Histone H2A variant dynamics during preimplantation development in mice (2010)
  • Author(s): Nashun B
  • Organizer: Cold Spring Harbor Symposium-Epigenetics, Chromatin & Transcription
  • Place of Presentation: Suzhou, China
  • Year and Date: 2010-05-19
• [Presentation] Involvement of histone variants replacement in the genome remodeling after fertilization International Symposium on (2010)
  • Author(s): Aoki, F
  • Organizer: Epigenome Network Development and Reprogramming of Germ Cells
  • Place of Presentation: Fukuoka
• [Presentation] The preferential incorporation of H2A.X into chromatin in early preimplantation embryos involves its C-terminal domain (2010)
  • Author(s): Nashun B, Aoki F
  • Organizer: 69th Annual Meeting of Society for Developmental Biology
  • Place of Presentation: Albuquerque
• [Presentation] Mechanism of global gene silencing and reactivation during oocyte growth at the one-cell stage after fertilization in mice (2010)
  • Author(s): Abe K , Aoki F
  • Organizer: 69th Annual Meeting of Society for Developmental Biology
  • Place of Presentation: Albuquerque
• [Presentation] Histone H2A variant dynamics during preimplantation development in mice Cold Spring Harbor Symposium -Epigenetics (2010)
  • Author(s): Nashun B, Yukawa M, Liu H, Akiyama T , Aoki F
  • Organizer: Chromatin & Transcription
  • Place of Presentation: Suzhou
• [Presentation] 受精前後におけるゲノム再プログラム化機構-ヒストン修飾および変異体置換の関与- (2009)
  • Author(s): 青木不学
  • Organizer: 第56回日本実験動物学会
  • Place of Presentation: 大宮
  • Year and Date: 2009-05-14
• [Presentation] 受精前後におけるゲノム再プログラム化機構-ピストン修飾および変異体置換の関与 (2009)
  • Author(s): 青木不学
  • Organizer: 第56回日本実験動物学会
  • Place of Presentation: 大宮
  • Year and Date: 2009-05-14
• [Presentation] マウス初期胚における遺伝子発現調節機構 (2009)
  • Author(s): 青木不学
  • Organizer: 第50回日本哺乳動物卵子学会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-08
• [Presentation] 卵形成および初期発生期におけるヒストンH3変異体の動態解析 (2008)
  • Author(s): 青木不学
  • Organizer: 「生殖細胞の発生プロセス・再プログラム化とエピジェネティクス」公開シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-24
• [Presentation] Dynamics of histone H3 variant deposition during oogenesis and preimplantation development (2008)
  • Author(s): Akiyama T, Nagata M, Aoki F
  • Organizer: World Congress on Reproductive Biology
  • Place of Presentation: Kailua-Kona
• [Presentation] Involvement of ATM in H2AX phosphorylation during early preimplantation development in mice (2008)
  • Author(s): Yukawa M, Nagata M, Aoki F
  • Organizer: 41th Annual meeting of Society for the Study of Reproduction
  • Place of Presentation: Kailua-Kona
• [Presentation] The contribution of germinal vesicle materials to the determination of developmental competence in mouse oocytes (2008)
  • Author(s): Inoue A, Nakajima R, Nagata M, Aoki F.
  • Organizer: 41th Annual meeting of Society for the Study of Reproduction
  • Place of Presentation: Kailua-Kona
• [Book] 受精前後の遺伝子発現プログラム、「卵子学」、森崇英編 (2011)
  • Author(s): 青木不学
  • Publisher: 京都大学
• [Book] (2011)
  • Author(s): 卵子学(共著・分担)
  • Publisher: 京都大学出版会
• [Book] 受精とリプログラミング.Medical Bio, 9 (2009)
  • Author(s): 青木不学
• [Remarks] 青木不学:卵のクオリティーについて.第19回セント・ルカセミナー、大分、2012年6月3日.