Functional analysis of novel histone H3 variant H3mm7 in skeletal muscle differentiation

• Project/Area Number: 15K18457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: Kyushu University
• Principal Investigator: HARADA AKIHITO 九州大学, 生体防御医学研究所, 助教 (60596823)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヒストンバリアント / 骨格筋分化 / エピジェネティクス

Outline of Final Research Achievements

The histone H3 variant H3.3 marks skeletal muscle specific genes in the undifferentiated state to provide selective gene expression during differentiation. Although some of the newly discovered histone variants have been shown to be highly expressed in skeletal muscle, their functions are still unknown. In this study, we performed functional analysis on one of these variants, H3mm7, in skeletal muscle. Using cultured cells, it was revealed that a rate change in gene expression occurs when H3mm7 is incorporated into the gene. In addition, the structure of the nucleosome containing H3mm7 was found to be less stable than the H3.3 nucleosome. These results together suggest that H3mm7 facilitates the expression of skeletal muscle genes by destabilizing nucleosomes at these genes to promote skeletal muscle differentiation.

Research Products

• [Journal Article] Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes/Macrophages after Spinal Cord Injury (2017)
  • Author(s): Yokota K, Kobayakawa K, Saito T, Hara M, Kijima K, Ohkawa Y, Harada A, Okazaki K, Ishihara K, Yoshida S, Kudo A, Iwamoto Y, Okada S.
  • Journal Title: Am J Pathol Volume: 187 Pages: 639-53
  • DOI: 10.1016/j.ajpath.2016.11.010
  • 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 Report Volume: 18(3) Pages: 593-600
  • DOI: 10.1016/j.celrep.2016.12.065
  • 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
  • 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: Scientific Reports Volume: 6 Pages: 24318-24318
  • DOI: 10.1038/srep24318
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chd5 regulates MuERV-L/MERVL expression in mouse embryonic stem cells via H3K27me3 modification and histone H3.1/H3.2. (2016)
  • Author(s): Hayashi M, Maehara K, Harada A, Semba Y, Kudo K, Takahashi H, Oki S, Meno C, Ichiyanagi K, Akashi K, Ohkawa Y.
  • Journal Title: J. Cell. Biochem. Volume: 117 Pages: 780-792
  • DOI: 10.1002/jcb.25368
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis (2016)
  • Author(s): Urahama T, Harada A, Maehara K, Horikoshi N, Sato K, Sato Y, Shiraishi K, Sugino N, Osakabe A, Tachiwana H, Kagawa W, Kimura H, Ohkawa Y, Kurumizaka H.
  • Journal Title: Epigenetics & Chromatin Volume: 9 Pages: 1-16
  • DOI: 10.1186/s13072-016-0051-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Distribution of histone H4 modifications as revealed by a panel of specific monoclonal antibodies. (2015)
  • Author(s): Hayashi-Takanaka Y., Maehara K., Harada A., Umehara T., Yokoyama S., Obuse C., Ohkawa Y., Nozaki N., Kimura H.
  • Journal Title: Chromosome Res Volume: 23 Pages: 735-766
  • DOI: 10.1007/s10577-015-9486-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Relationship between the risk for a shrimp allergy and freshness or cooking. (2015)
  • Author(s): Masakatsu USUI, Akihito HARADA, Shinya YASUMOTO, Yoshimasa SUGIURA, Anri NISHIDAI, Maria IKARASHI, Honami TAKABA, Taiko MIYASAKI, Hiroyuki AZAKAMI, and Masakazu KONDO
  • Journal Title: Biosci Biotechnol Biochem. Volume: 未定 Pages: 1698-1701
  • DOI: 10.1080/09168451.2015.1045830
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tissue-specific expression of histone H3 variants diversified after species separation. (2015)
  • Author(s): Maehara K, Harada A, Sato Y, Matsumoto M, Nakayama KI, Kimura H, Ohkawa Y.
  • Journal Title: Epigenetics Chromatin. Volume: 8 Pages: 1-17
  • DOI: 10.1186/s13072-015-0027-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 急性期の筋萎縮過程における遺伝子発現変動解析 (2017)
  • Author(s): 原田 哲仁，岩崎 健，横田 和也，岡田 誠司，大川 恭行
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大（京都府）
  • Year and Date: 2017-03-17
• [Presentation] Functional switching of histone H3 variants in myogenesis (2017)
  • Author(s): 原田哲仁
  • Organizer: 第4回ヒストンバリアント研究会
  • Place of Presentation: 東北大学青葉山新キャンパス 青葉山コモンズ
  • Invited
• [Presentation] エピジェネティック破綻により引き起こされた筋肉腫の解析 (2017)
  • Author(s): 原田哲仁
  • Organizer: 公益財団法人福岡県すこやか健康事業団平成28年度がん研究助成金優秀賞受賞講演
  • Place of Presentation: 西鉄グランドホテル（福岡県福岡市）
  • Invited
• [Presentation] ヒストンH3バリアントの発現変動は筋萎縮過程の初期イベントである (2016)
  • Author(s): 原田 哲仁, 岩崎 健, 横田 和也, 岡田 誠司, 大川 恭行
  • 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] 骨格筋分化におけるクロマチン構造解析-トランスクリプトミクスで理解する骨格筋形成 (2016)
  • Author(s): 原田哲仁
  • Organizer: 日本農芸化学会中四国支部 支部創立15周年記念 第24回若手シンポジウム
  • Place of Presentation: 水産大学校 (山口県下関市)
  • Year and Date: 2016-07-28
  • Invited
• [Presentation] 新規ヒストンH3バリアントH3mm7は骨格筋分化能を制御する (2016)
  • Author(s): 原田 哲仁
  • Organizer: 日本農芸化学会 2016 大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-29
• [Presentation] 新規ヒストンH3バリアントH3mm7は骨格筋分化能を制御する (2015)
  • Author(s): 原田 哲仁
  • Organizer: 第38回日本分子生物学年会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-12-01
• [Presentation] ヒストンバリアントが制御する骨格筋分化能 (2015)
  • Author(s): 原田 哲仁、前原 一満、大川 恭行
  • Organizer: NGS現場の会第四回研究会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2015-07-01
  • Invited
• [Book] ヒストンバリアントによるエピゲノム制御 (2015)
  • Author(s): 原田 哲仁
  • Total Pages: 4
  • Publisher: ㈱メディカルレビュー社
• [Remarks] トランスクリプトミクス分野 ／ 大川研究室
  • URL: http://tx.bioreg.kyushu-u.ac.jp/
• [Patent(Industrial Property Rights)] DNA結合タンパク質の結合領域の近傍に所望のDNA断片を挿入する方法 (2016)
  • Inventor(s): 大川恭行,原田哲仁,胡桃坂仁志,木村宏,半田哲也,他2名
  • Industrial Property Rights Holder: 国立大学法人九州大学、国立大学法人東京工業大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-167967
  • Filing Date: 2016-08-30
  • Application Year: 2016