Functional analyses of testis-specific histone H3 variant H3t

• Project/Area Number: 16K07099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Asahikawa Medical College (2017-2018); Chubu University (2016)
• Principal Investigator: Ueda Jun 旭川医科大学, 医学部, 准教授 (80450394)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: クロマチン / ヒストンバリアント / 精子形成過程 / 無精子症 / エピジェネティクス / 精子形成 / ヒストンコード

Outline of Final Research Achievements

We have identified that testis-specific histone H3 variant H3t is essential for spermatogenesis. When H3t gene was knocked out in mice, male became sterile, displaying azoospermia. Interestingly, although H3t protein was expressed in testicular tissues, this protein was absent from mature spermatozoa. Therefore, H3t is a histone that is only required during spermatogenesis. In this study, we have further investigated how H3t functions within the genome, together with other interacting proteins, to organize higher order chromatin structures during spermatogenesis.

Academic Significance and Societal Importance of the Research Achievements

我が国は現在未曾有の少子高齢化・人口減少に直面しており、人手不足など、問題の一部は既に顕在化している。この原因として、我が国全体で起こっている不妊症が考えられる。2015年現在、5.5組に1組が不妊の検査や治療を受けており、その半分は男性側が原因である。本研究成果は現段階では基礎研究の範疇ではあるが、本研究を通じて明らかになった知見は、最終的には臨床医との共同研究を通じて男性不妊症の診断法や治療法の開発に繋げたいと考えている。特に、我が国において生殖補助医療（体外受精、顕微授精など）によって産まれてくる児は約20人に1人となっていることから、生殖補助医療の成功率を上げることが重要と考えている。

Research Products

• [Int'l Joint Research] University of Toronto(カナダ)
• [Int'l Joint Research] National University of Singapore/Cancer Science Institute of Singapore(シンガポール)
• [Int'l Joint Research] University of Toronto/Structural Genomics Consortium(カナダ)
• [Int'l Joint Research] シンガポールがん科学研究所/シンガポール国立大学(シンガポール)
• [Journal Article] Pathways of Progression From Intraductal Papillary Mucinous Neoplasm to Pancreatic Ductal Adenocarcinoma Based on Molecular Features (2019)
  • Author(s): Omori Y, Ono Y, Tanino M, Karasaki H, Yamaguchi H, Furukawa T, Enomoto K, Ueda J, Sumi A, Katayama J, Muraki M, Taniue K, Takahashi K, Ambo Y, Shinohara T, Nishihara H, Sasajima J, Maguchi H, Mizukami Y*, Okumura T, Tanaka S.
  • Journal Title: Gastroenterology Volume: 156 Issue: 3 Pages: 647-661
  • DOI: 10.1053/j.gastro.2018.10.029
  • Peer Reviewed / Open Access
• [Journal Article] A microfluidic device for isolating intact chromosomes from single mammalian cells and probing their folding stability by controlling solution conditions (2018)
  • Author(s): T. Takahashi, K. O. Okeyo, J. Ueda, K. Yamagata, M. Washizu, H. Oana
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 13684-13684
  • DOI: 10.1038/s41598-018-31975-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The normality of sperm in an infertile man with ring chromosome 15: a case report. (2018)
  • Author(s): Nishikawa K, Itoi F, Nagahara M, Jose M, Matsunaga A, Ueda J, Iwamoto T.
  • Journal Title: J Assist Reprod Genet. Volume: 35 Issue: 2 Pages: 251-256
  • DOI: 10.1007/s10815-017-1061-9
  • Peer Reviewed / Open Access
• [Journal Article] Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells (2017)
  • Author(s): Semba Yuichiro、Harada Akihito、Maehara Kazumitsu、Oki Shinya、Meno Chikara、Ueda Jun、Yamagata Kazuo、Suzuki Atsushi、Onimaru Mitsuho、Nogami Jumpei、Okada Seiji、Akashi Koichi、Ohkawa Yasuyuki
  • Journal Title: Nucleic Acids Research Volume: 45 Issue: 15 Pages: 8758-8772
  • DOI: 10.1093/nar/gkx475
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of the H3K9 methyltransferase G9A attenuates oncogenicity and activates the hypoxia signaling pathway. (2017)
  • Author(s): Ho JC, Abdullah LN, Pang QY, Jha S, Chow EK, Yang H, Kato H, Poellinger L, Ueda J, Lee KL.
  • Journal Title: PLoS One Volume: 12 Issue: 11 Pages: e0188051-e0188051
  • DOI: 10.1371/journal.pone.0188051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extraction of Cell Nuclei using CNN Features (2017)
  • Author(s): Tsukada Y., Iwahori Y. Funahashi K. Jose M. Ueda J. Iwamoto T.
  • Journal Title: Procedia Computer Science Volume: 112 Pages: 1633-1640
  • DOI: 10.1016/j.procs.2017.08.255
  • Peer Reviewed / Open Access
• [Journal Article] Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis (2017)
  • Author(s): Ueda J., Harada A., Urahama T., Machida S., Maehara K., Hada M., Makino Y., Nogami J., Horikoshi N., Osakabe A., Taguchi H., Tanaka H., Tachiwana H., Yao T., Yamada M., Iwamoto T., Isotani A., Ikawa M., Tachibana T., Okada Y., Kimura H., Ohkawa Y., Kurumizaka H., Yamagata K.
  • Journal Title: Cell Reports Volume: 18(3) Issue: 3 Pages: 593-600
  • DOI: 10.1016/j.celrep.2016.12.065
  • NAID: 120006957416
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation. (2017)
  • Author(s): Yamaguchi L, Nishiyama A, Misaki T, Johmura Y, Ueda J, Arita K, Nagao K, Obuse C, Nakanishi M
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-017-00136-5
  • Peer Reviewed / Open Access
• [Journal Article] A genetically encoded probe for live-cell imaging of H4K20 monomethylation (2016)
  • Author(s): Sato Y., Kujirai T., Arai R., Asakawa H., Ohtsuki C., Horikoshi N., Yamagata K., Ueda J., Nagase T., Haraguchi T., Hiraoka Y., Kimura A., Kurumizaka H., Kimura, H.
  • Journal Title: J. Mol. Biol. Volume: 428 Issue: 20 Pages: 3885-3902
  • DOI: 10.1016/j.jmb.2016.08.010
  • Peer Reviewed / Open Access
• [Presentation] A granular parakeratosis animal model created by topical aluminum showed characteristic keratinocyte differentiation abnormalities including abnormal profilaggrin processing and cornified cell envelop formation (2018)
  • Author(s): Fujii, M., Kishibe, M., Ueda, J., Hitomi, K., and Ishida-Yamamoto, A.
  • Organizer: International Investigative Dermatology 2018
  • Int'l Joint Research
• [Presentation] Diversity of precursor lesions for pancreatic cancer: Genetics and biology of intraductal papillary mucinous neoplasm (2018)
  • Author(s): Yusuke Mizukami, Yusuke Ono, Hidenori Karasaki, Yuko Omori, Jun Ueda, Toshikatsu Okumura.
  • Organizer: The 77th Annual Meeting of the Japanese Cancer Association
• [Presentation] ラット体外受精卵を用いたエレクトロポレーションによるゲノム編集動物の作製 (2018)
  • Author(s): 日野千紘，藤倉大輔，上田潤，船越洋
  • Organizer: 第52回日本実験動物技術者協会総会
• [Presentation] CNN特徴量を利用した明視野画像からの細胞核抽出 (2017)
  • Author(s): 塚田裕也，岩堀祐之，舟橋健司，上田潤，岩本隆司
  • Organizer: 第42回東海ファジィ研究会in日間賀島（ヒマ研2017）
  • Place of Presentation: 日間賀島公民館，愛知県，南知多町
  • Year and Date: 2017-02-19
• [Presentation] Testis-Specific Histone Variant H3t Gene is Essential for Entry into Spermatogenesis. (2017)
  • Author(s): Jun Ueda
  • Organizer: Society for the Study of Reproduction 2017 Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] 1細胞・染色体単離技術に基づいた細胞の分化度と染色体構造安定性との相関の解析 (2017)
  • Author(s): 高橋智博, オケヨ ケネディ, 上田潤, 鷲津正夫, 小穴英廣
  • Organizer: 化学とマイクロ・ナノシステム学会 第35回研究会（35th CHEMINAS）
• [Presentation] 精巣特異的ヒストンバリアント H3t は精子幹細胞の精子形成過程への移行に必須である (2017)
  • Author(s): 山縣一夫，上田潤，原田哲仁，浦浜嵩，町田晋一，前原一満，羽田政司，牧野吉倫，野上順平，堀越直樹，越阪部晃永，田口裕之，田中大貴，立和名博昭，八尾竜馬，山田みなみ，岩本隆司，磯谷綾子，伊川正人，立花太郎，岡田由紀，木村宏，大川恭行，胡桃坂仁志
  • Organizer: 第35回日本受精着床学会総会・学術講演会
  • Invited
• [Presentation] 単一ES細胞の分化分裂過程におけるメチル化DNA動態の定量的観察 (2017)
  • Author(s): 穂井田謙介，上田潤，池田善貴，古谷駿治，野老美紀子，細井美彦，山縣一夫
  • Organizer: 第35回日本受精着床学会総会・学術講演会
• [Presentation] Extraction of Cell Nuclei using CNN Features. (2017)
  • Author(s): Tsukada, Y., Iwahori, Y., Funahashi, K., Jose, M., Ueda, J., and Iwamoto, T.
  • Organizer: 21st International Conference on Knowledge Based and Intelligent Information and Engineering Systems, KES2017
  • Int'l Joint Research
• [Presentation] Direct Observation-based Analysis of Compaction Stability of Individual Chromosomes isolated from Single Mammalian Cells (2017)
  • Author(s): Oana, H., Takahashi, T., Okeyo, K.O., Ueda, J., and Washizu, M.
  • Organizer: 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2017)
  • Int'l Joint Research
• [Presentation] マイクロRNA導入マウスに発症した拡張型心筋症における還元ストレスの解析 (2017)
  • Author(s): 小川剛汰，松山留美子，喬善楼，小形岳寛，上田潤，岩本隆司
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] メチローマウスを用いた腫瘍分類の画像解析 (2017)
  • Author(s): 上瀬茉美，高橋幸司，中島妙子，八尾竜馬，岩本隆司，上田潤
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 単一ES細胞の分化分裂過程におけるメチル化DNA動態の観察法の検討 (2017)
  • Author(s): 池田善貴，穂井田謙介，上田潤，古谷駿治，野老美紀子，細井美彦，山縣一夫
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] マイクロ流路を用いた細胞の分化度と染色体構造安定性との相関のリアルタイム解析技術開発 (2017)
  • Author(s): 小穴英廣，高橋智博，Kennedy Okeyo，上田潤，山縣一夫，鷲津正夫
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] メチローマウス由来単一ES細胞におけるメチル化DNA動態の動的観察法の開発 (2016)
  • Author(s): 穂井田謙介，上田潤，財田大地，山田健，野老美紀子，細井美彦，山縣 一夫
  • Organizer: 第39回日本分生生物学会年
  • Place of Presentation: パシフィコ横浜，神奈川，横浜市
  • Year and Date: 2016-11-30
• [Presentation] クロマチンリモデリング因子Chd2はマウスES細胞の分化能維持に必須である (2016)
  • Author(s): 仙波雄一郎，原田哲仁，前原一満，小田原淳，工藤健介，岩崎健史，沖真弥，目野主税，上田潤，山縣一夫，大川恭行
  • Organizer: 第39回日本分生生物学会年会
  • Place of Presentation: パシフィコ横浜，神奈川，横浜市
  • Year and Date: 2016-11-30
• [Presentation] Hypoxia Mediated Epigenetics and Their Function in the Cell Survival Response of Cancer Cells. (2016)
  • Author(s): Lee, K.L., Ho, J.C., Ueda, J., Kitajima, S., Sun, W., Jia, Y., Chia, G.S., Zaiden, N., Yit, L.Y., Leong, Y.S., Tham, C.F.Y., Han, J., Pang, Q.Y., Fukuhara, N., Oba, H., Yang, H., Kato, H., and Poellinger, L.
  • Organizer: 第14回がんとハイポキシア研究会
  • Place of Presentation: 岐阜グランドホテル，岐阜県，岐阜市
  • Year and Date: 2016-11-04
• [Presentation] Hypoxia Mediates Tumourigenesis via the H3K9 Epigenetic Regulators G9A and JMJD1A. (2016)
  • Author(s): Ho, J.C., Ueda, J., Lee, K.L., and Poellinger, L.
  • Organizer: 第14回がんとハイポキシア研究会
  • Place of Presentation: 岐阜グランドホテル，岐阜県，岐阜市
  • Year and Date: 2016-11-04
• [Presentation] Direct acquisition of genome-wide epigenetic information along intact chromatin fibers of individual chromosomes isolated from single mammalian cells. (2016)
  • Author(s): Takahashi, T., Okeyo, K.O., Washizu, M., Ueda, J., and Oana, H.
  • Organizer: The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences
  • Place of Presentation: Dublin, Ireland.
  • Year and Date: 2016-10-09
  • Int'l Joint Research
• [Presentation] Direct Observation of Epigenetic Modifications along Intact Chromatin Fibers of Individual Chromosomes Isolated from Single Cells in a Microfluidic Channel. (2016)
  • Author(s): Takahashi, T., Okeyo, K.O., Washizu, M., Ueda, J., and Oana, H.
  • Organizer: 2016 International Conference on Solid State Devices and Materials
  • Place of Presentation: つくば国際会議場，茨城県，つくば市
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] 動物細胞クロマチンファイバーに対する化学修飾および凝縮部の光マッピング (2016)
  • Author(s): 高橋智博，オケヨ ケネディ，鷲津正夫，上田潤，小穴英廣
  • Organizer: 化学とマイクロ・ナノシステム学会第34回研究会
  • Place of Presentation: 幕張メッセ国際会議場，千葉県，千葉市
  • Year and Date: 2016-09-06
• [Presentation] Testis-Specific Histone Variant H3t is Essential for Entry into Spermatogenesis. (2016)
  • Author(s): Ueda, J., Harada, A., Urahama, T., Machida, S., Maehara, K., Horikoshi, N., Osakabe, A., Taguchi, H., Tanaka, H., Tachiwana, H., Yao, T., Isotani, A., Ikawa, M., Tachibana, T., Kimura, H., Ohkawa, Y., Kurumizaka, H., and Yamagata, K.
  • Organizer: Cold Spring Harbor Asia ‘Chromatin, Epigenetics and Transcription’
  • Place of Presentation: Suzhou, China.
  • Year and Date: 2016-05-09
  • Int'l Joint Research
• [Book] 細胞 (2018)
  • Author(s): 上田潤，水上裕輔，大栗敬幸
  • Total Pages: 5
  • Publisher: ニューサイエンス社
• [Book] 肝胆膵 (2018)
  • Author(s): 河端秀賢，水上裕輔，岡田哲弘，佐藤裕基，林明宏，後藤拓磨，笹島順平，高氏修平，上田潤，小野裕介，唐崎秀則，奥村利勝
  • Total Pages: 7
  • Publisher: アークメディア社
• [Book] Precision Medicine (2018)
  • Author(s): 小山恭平，上田潤，紙谷寛之
  • Total Pages: 6
  • Publisher: 北隆館
• [Book] 細胞 (2017)
  • Author(s): 上田潤，大栗敬幸．
  • Total Pages: 5
  • Publisher: ニューサイエンス社
• [Remarks]
  • URL: https://researchmap.jp/wiz/?lang=japanese
• [Remarks]
  • URL: https://researchmap.jp/wiz/
• [Remarks]
  • URL: http://researchmap.jp/wiz/?lang=japanese