Analysis of biological functions of novel histone variants

• Project/Area Number: 16K18479
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: System genome science
• Research Institution: Kyushu University
• Principal Investigator: Maehara Kazumitsu 九州大学, 生体防御医学研究所, 助教 (90726431)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヒストンバリアント / エピゲノム制御 / ヒストンコード / クロマチン

Outline of Final Research Achievements

This project aimed to recognize the function of the novel histone variants in cell differentiation. In the mouse genome, we previously identified fourteen hitherto unknown H3 genes of which thirteen are analogous to H3.3, and reported that some of these genes were expressed in skeletal muscle. We demonstrated that one such histone H3 variant H3mm7 is preferentially expressed in quiescent satellite cells and that it is essential for myogenesis. Further chromatin analysis unveiled that H3mm7 was incorporated into the promoter regions of active gene loci including myogenic genes and that it was required for open chromatin structure to facilitate transcription. These results were published as well as three reports on human histone variants in our joint research projects.

Research Products

• [Journal Article] Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration (2018)
  • Author(s): Harada Akihito、Maehara Kazumitsu、Ono Yusuke、Taguchi Hiroyuki、Yoshioka Kiyoshi、Kitajima Yasuo、Xie Yan、Sato Yuko、Iwasaki Takeshi、Nogami Jumpei、Okada Seiji、Komatsu Tetsuro、Semba Yuichiro、Takemoto Tatsuya、Kimura Hiroshi、Kurumizaka Hitoshi、Ohkawa Yasuyuki
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1400-1400
  • DOI: 10.1038/s41467-018-03845-1
  • NAID: 120006949474
  • Peer Reviewed / Open Access
• [Journal Article] Cryo-EM structure of the nucleosome containing the ALB1 enhancer DNA sequence (2018)
  • Author(s): Takizawa Yoshimasa、Tanaka Hiroki、Machida Shinichi、Koyama Masako、Maehara Kazumitsu、Ohkawa Yasuyuki、Wade Paul A.、Wolf Matthias、Kurumizaka Hitoshi
  • Journal Title: Open Biology Volume: 8 Issue: 3 Pages: 170255-170255
  • DOI: 10.1098/rsob.170255
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sensitive detection of fluorescence in western blotting by merging images (2018)
  • Author(s): Kondo Yukari、Higa Shinichiro、Iwasaki Takeshi、Matsumoto Tomoya、Maehara Kazumitsu、Harada Akihito、Baba Yoshihiro、Fujita Masatoshi、Ohkawa Yasuyuki
  • Journal Title: PLOS ONE Volume: 13 Issue: 1 Pages: 0191532-0191532
  • DOI: 10.1371/journal.pone.0191532
  • Peer Reviewed / Open Access
• [Journal Article] The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation (2017)
  • Author(s): Kudou Kensuke、Komatsu Tetsuro、Nogami Jumpei、Maehara Kazumitsu、Harada Akihito、Saeki Hiroshi、Oki Eiji、Maehara Yoshihiko、Ohkawa Yasuyuki
  • Journal Title: Open Biology Volume: 7 Issue: 9 Pages: 170119-170119
  • DOI: 10.1098/rsob.170119
  • 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] Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8 (2017)
  • Author(s): Taguchi H, Xie Y, Horikoshi N, Maehara K, Harada A, Nogami J, Sato K, Arimura Y, Osakabe A, Kujirai T, Iwasaki T, Semba Y, Tachibana T, Kimura H, Ohkawa Y, Kurumizaka H.
  • Journal Title: Biochemistry Volume: 56 Issue: 16 Pages: 2184-2196
  • DOI: 10.1021/acs.biochem.6b01098
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thymine DNA glycosylase modulates the DNA damage response and gene expression by base excision repair-dependent and -independent mechanisms (2017)
  • Author(s): Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, and Kaoru Sugasawa
  • Journal Title: Genes to Cells Volume: 22 Issue: 4 Pages: 392-405
  • DOI: 10.1111/gtc.12481
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Crystal structure of the overlapping dinucleosome composed of hexasome and octasome (2017)
  • Author(s): Daiki Kato, Akihisa Osakabe, Yasuhiro Arimura, Yuka Mizukami, Naoki Horikoshi, Kazumi Saikusa, Satoko Akashi, Yoshifumi Nishimura, Sam-Yong Park, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Atsushi Matsumoto, Hidetoshi Kono, Rintaro Inoue, Masaaki Sugiyama, Hitoshi Kurumizaka
  • Journal Title: Science Volume: 356 Issue: 6334 Pages: 205-208
  • DOI: 10.1126/science.aak9867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Identification of Immunoglobulin Gene Sequences from a Small Read Number of mRNA-Seq Using Hybridomas. (2016)
  • Author(s): Kuniyoshi Y, Maehara K, Iwasaki T, Hayashi M, Semba Y, Fujita M, Sato Y, Kimura H, Harada A, Ohkawa Y.
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0165473-e0165473
  • DOI: 10.1371/journal.pone.0165473
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells. (2016)
  • Author(s): Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., and Isaka, Y.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 24318-24318
  • DOI: 10.1038/srep24318
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing (2016)
  • Author(s): Kobayashi W., Takaku M., Machida S., Tachiwana H., Maehara K., Ohkawa Y. and Kurumizaka H
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 24428-24428
  • DOI: 10.1038/srep24228
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ヒストンH3.3のサブバリアントH3mm7は正常な骨格筋再生に必要とされる (2017)
  • Author(s): 前原 一満
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Myogenic Chromatin Structure Is Formed with the Histone H3 Variant H3mm7 (2017)
  • Author(s): Kazumitsu Maehara, Akihito harada, Jumpei Nogami, Yasuyuki Ohkawa
  • Organizer: 第20回生医研リトリート2017
• [Presentation] ホッジ分解による擬似ライブ・シングルセルプロファイル追跡法 (2016)
  • Author(s): 前原一満
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Remarks] Ohkawa lab.
  • URL: http://tx.bioreg.kyushu-u.ac.jp
• [Remarks] プレスリリース「筋肉の再生を促進させるスイッチの発見-筋肉の再生治療の応用に期待-」
  • URL: https://www.kyushu-u.ac.jp/ja/researches/view/235
• [Remarks] 研究室HP
  • URL: http://tx.bioreg.kyushu-u.ac.jp
• [Patent(Industrial Property Rights)] 標的遺伝子の配列を決定する方法 (2017)
  • Inventor(s): 大川恭行、前原一満、木村宏、佐藤優子
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-03-16
  • Overseas