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Elucidation of the mechanism of transcription elongation rate control by histone code

Research Project

Project/Area Number 17H04035
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionTohoku University

Principal Investigator

NAKAYAMA Keiko  東北大学, 医学系研究科, 教授 (60294972)

Co-Investigator(Kenkyū-buntansha) 城田 松之  東北大学, 医学系研究科, 講師 (00549462)
舟山 亮  東北大学, 医学系研究科, 助教 (20452295)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsヒストン修飾 / RNAポリメラーゼ / 修飾酵素 / H3K27me3 / H3K36me3 / DRB
Outline of Final Research Achievements

To measure the rate of transcription elongation, we used DRB treatment, an RNA polymerase inhibitor, and BrU labeling of the newly synthesized RNAs to recover the newly synthesized RNAs. We measured the elongation rate of model genes, such as the highly transcribed GAPDH gene. To determine how H3K27me3 modification affects the elongation rate of RNA polymerase in cells, cells were knocked down with SUZ12 and reduced H3K27me3 modification, resulting that H3K27me3 modification is negatively correlated with the elongation rate of transcription.
Now, to investigate the comprehensiveness of this phenomenon, we performed RNA seq of a newly synthesized RNA and ChIP seq of H3K27me3.

Academic Significance and Societal Importance of the Research Achievements

生物の遺伝情報は、ゲノムDNAに書き込まれているが、その情報をどのように読み出しているのかについて、様々な制御が存在していることが知られている。本研究では、特にゲノムDNAが結合しているヒストンタンパク質の状態が、RNAとして読み出される過程にどのような影響を与えているのかを、実際の読み出し速度を測定することで検証を行った。その結果、ヒストンの修飾は、読み出し量と同時に、その速度に影響を与えていることを明らかとすることができた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (33 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (24 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 24 results,  Open Access: 15 results) Presentation (6 results) Remarks (3 results)

  • [Journal Article] Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study2021

    • Author(s)
      Hozawa A, Tanno K, Nakaya N, Nakamura T, Tsuchiya N, Hirata T, Narita A, Kogure M, Nochioka K, Sasaki R, Takanashi N, Otsuka K, Sakata K, Kuriyama S, Kikuya M, 13名略, Kobayashi T, 53名略, Yamamoto M.
    • Journal Title

      Journal of Epidemiology

      Volume: 31 Issue: 1 Pages: 65-76

    • DOI

      10.2188/jea.JE20190271

    • NAID

      130007966030

    • ISSN
      0917-5040, 1349-9092
    • Year and Date
      2021-01-05
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice2020

    • Author(s)
      Wada Yoichi、Kikuchi Atsuo、Kaga Akimune、Shimizu Naoki、Ito Junya、Onuma Ryo、Fujishima Fumiyoshi、Totsune Eriko、Sato Ryo、Niihori Tetsuya、Shirota Matsuyuki、Funayama Ryo、Sato Kota、Nakazawa Toru、Nakayama Keiko、Aoki Yoko、Aiba Setsuya、Nakagawa Kiyotaka、Kure Shigeo
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 2 Pages: e1008628-e1008628

    • DOI

      10.1371/journal.pgen.1008628

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis.2020

    • Author(s)
      Masamune A, Kotani H, Sorgel FL, Chen JM, Hamada S, Sakaguchi R, Masson E, Nakano E, et al.
    • Journal Title

      Gastroenterology

      Volume: - Issue: 6 Pages: 1626-1641

    • DOI

      10.1053/j.gastro.2020.01.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial-Mesenchymal Transition2020

    • Author(s)
      Sato Masaki、Matsumoto Mitsuyo、Saiki Yuriko、Alam Mahabub、Nishizawa Hironari、Rokugo Masahiro、Brydun Andrey、Yamada Shinji、Kaneko Mika K.、Funayama Ryo、Ito Mamoru、Kato Yukinari、Nakayama Keiko、Unno Michiaki、Igarashi Kazuhiko
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 6 Pages: 1279-1292

    • DOI

      10.1158/0008-5472.can-18-4099

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components.2020

    • Author(s)
      Nakagawa T, Nakayama K, Nakayama KI.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1217 Pages: 147-171

    • DOI

      10.1007/978-981-15-1025-0_10

    • ISBN
      9789811510243, 9789811510250
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): Rationale, progress and perspective2020

    • Author(s)
      Kuriyama S, Metoki H, Kikuya M, Obara T, Ishikuro M, Yamanaka C, Nagai M, Matsubara H, Kobayashi T, 57名略, Yamamoto M.
    • Journal Title

      Int J Epidemiol.

      Volume: 49 Issue: 1 Pages: 18

    • DOI

      10.1093/ije/dyz169

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome2019

    • Author(s)
      Niitsuma Sou、Kudo Hiroki、Kikuchi Atsuo、Hayashi Takaya、Kumakura Satoshi、Kobayashi Shuhei、Okuyama Yuko、Kumagai Naonori、Niihori Tetsuya、Aoki Yoko、So Takanori、Funayama Ryo、Nakayama Keiko、Shirota Matsuyuki、Kondo Shuji、Kagami Shoji、Tsukaguchi Hiroyasu、Iijima Kazumoto、Kure Shigeo、Ishii Naoto
    • Journal Title

      International Immunology

      Volume: 32 Issue: 4 Pages: 283-292

    • DOI

      10.1093/intimm/dxz081

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathogenic mutations in the ALS gene CCNF cause cytoplasmic mislocalization of Cyclin F and elevated VCP ATPase activity.2019

    • Author(s)
      Yu Y, Nakagawa T, Morohoshi A, Nakagawa M, Ishida N, Suzuki N, Aoki M, Nakayama K.
    • Journal Title

      Hum Mol Genet

      Volume: 28 Issue: 20 Pages: 3486-3497

    • DOI

      10.1093/hmg/ddz119

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of NRAS mutation in cell-free DNA biological fluids from patients with kaposiform lymphangiomatosis2019

    • Author(s)
      Ozeki Michio、Aoki Yoko、Nozawa Akifumi、Yasue Shiho、Endo Saori、Hori Yumiko、Matsuoka Kentaro、Niihori Tetsuya、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Fukao Toshiyuki
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 14 Issue: 1 Pages: 215-215

    • DOI

      10.1186/s13023-019-1191-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer‐associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer2019

    • Author(s)
      Aizawa Takashi、Karasawa Hideaki、Funayama Ryo、Shirota Matsuyuki、Suzuki Takashi、Maeda Shimpei、Suzuki Hideyuki、Yamamura Akihiro、Naitoh Takeshi、Nakayama Keiko、Unno Michiaki
    • Journal Title

      Cancer Medicine

      Volume: 8 Issue: 14 Pages: 6370-6382

    • DOI

      10.1002/cam4.2523

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons.2019

    • Author(s)
      Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J, Funayama R, Fujishima F, Mitsuzawa S, Ikeda K, Ono H, Shijo T, Osana S, Shirota M, Nakagawa T, et al.
    • Journal Title

      EBioMedicine

      Volume: 45 Pages: 362-378

    • DOI

      10.1016/j.ebiom.2019.06.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germline-Activating RRAS2 Mutations Cause Noonan Syndrome2019

    • Author(s)
      Niihori Tetsuya、Nagai Koki、Fujita Atsushi、Ohashi Hirofumi、Okamoto Nobuhiko、Okada Satoshi、Harada Atsuko、Kihara Hirotaka、Arbogast Thomas、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Abe Taiki、Inoue Shin-ichi、Tsai I-Chun、Matsumoto Naomichi、Davis Erica E.、Katsanis Nicholas、Aoki Yoko
    • Journal Title

      The American Journal of Human Genetics

      Volume: 104 Issue: 6 Pages: 1233-1240

    • DOI

      10.1016/j.ajhg.2019.04.014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent de novo MAPK8IP3 variants cause neurological phenotypes2019

    • Author(s)
      Iwasawa Shinya、Yanagi Kumiko、Kikuchi Atsuo、Kobayashi Yasuko、Haginoya Kazuhiro、Matsumoto Hiroshi、Kurosawa Kenji、Ochiai Masayuki、Sakai Yasunari、Fujita Atsushi、Miyake Noriko、Niihori Tetsuya、ら
    • Journal Title

      Annals of Neurology

      Volume: - Issue: 6 Pages: 927-933

    • DOI

      10.1002/ana.25481

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The ubiquitin ligase subunit β-TrCP in Sertoli cells is essential for spermatogenesis in mice.2019

    • Author(s)
      Morohoshi, A., Nakagawa, T., Nakano, S., Nagasawa, Y., Nakayama, K.
    • Journal Title

      Dev Biol.

      Volume: 445 Issue: 2 Pages: 178-188

    • DOI

      10.1016/j.ydbio.2018.10.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum2018

    • Author(s)
      Abe Yuichi、Honsho Masanori、Itoh Ryota、Kawaguchi Ryoko、Fujitani Masashi、Fujiwara Kazushirou、Hirokane Masaaki、Matsuzaki Takashi、Nakayama Keiko、Ohgi Ryohei、Marutani Toshihiro、Nakayama Keiichi I、Yamashita Toshihide、Fujiki Yukio
    • Journal Title

      Life Science Alliance

      Volume: 1 Issue: 6 Pages: 1-17

    • DOI

      10.26508/lsa.201800062

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bach2 Promotes B Cell Receptor?Induced Proliferation of B Lymphocytes and Represses Cyclin-Dependent Kinase Inhibitors2018

    • Author(s)
      Miura Yuichi、Morooka Mizuho、Sax Nicolas、Roychoudhuri Rahul、Itoh-Nakadai Ari、Brydun Andrey、Funayama Ryo、Nakayama Keiko、Satomi Susumu、Matsumoto Mitsuyo、Igarashi Kazuhiko、Muto Akihiko
    • Journal Title

      J Immunol

      Volume: - Issue: 8 Pages: 2882-2893

    • DOI

      10.4049/jimmunol.1601863

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bone marrow PDGFRa+Sca-1+ enriched mesenchymal stem cells support survival of and antibody production by plasma cells in vitro through IL-6.2018

    • Author(s)
      Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, and Toshiyuki Takai.
    • Journal Title

      Int Immu

      Volume: in press Issue: 6 Pages: 241-253

    • DOI

      10.1093/intimm/dxy018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rett-like features and cortical visual impairment in a Japanese patient with HECW2 mutation2018

    • Author(s)
      Nakamura Haruhiko、Uematsu Mitsugu、Numata-Uematsu Yurika、Abe Yu、Endo Wakaba、Kikuchi Atsuo、Takezawa Yusuke、Funayama Ryo、Shirota Matsuyuki、Nakayama Keiko、Niihori Tetsuya、Aoki Yoko、Haginoya Kazuhiro、Kure Shigeo
    • Journal Title

      Brain Dev

      Volume: 40 Issue: 5 Pages: 410-414

    • DOI

      10.1016/j.braindev.2017.12.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.2018

    • Author(s)
      Nakagawa T, Hosogane M, Nakagawa M, Morohoshi A, Funayama R, Nakayama K.
    • Journal Title

      Mol Cell Biol

      Volume: 38 Issue: 5

    • DOI

      10.1128/mcb.00449-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucose deprivation induces primary cilium formation through mTORC1 inactivation2018

    • Author(s)
      Takahashi, K.、Nagai, T.、Chiba, S.、Nakayama, K.、and Mizuno. K.
    • Journal Title

      J Cell Sci

      Volume: 131 Issue: 1 Pages: 208769-208769

    • DOI

      10.1242/jcs.208769

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inferring evolutionary responses of Anolis carolinensis introduced into the Ogasawara archipelago using whole genome sequence data2017

    • Author(s)
      Tamate Satoshi、Iwasaki Watal M.、Krysko Kenneth L.、Camposano Brian J.、Mori Hideaki、Funayama Ryo、Nakayama Keiko、Makino Takashi、Kawata Masakado
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 18008-18008

    • DOI

      10.1038/s41598-017-17852-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis.2017

    • Author(s)
      Fukushima H, Shimizu K, Watahiki A, Hoshikawa S, Kosho T, Oba D, Sakano S, Arakaki M
    • Journal Title

      Mol Cell

      Volume: Nov 16;68(4) Issue: 4 Pages: 645-658

    • DOI

      10.1016/j.molcel.2017.10.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells.2017

    • Author(s)
      Nakagawa T, Zhang T, Kushi R, Nakano S, Endo T, Nakagawa M, Yanagihara N, Zarkower D, Nakayama K.
    • Journal Title

      Development

      Volume: 144 Pages: 4137-4147

    • DOI

      10.1242/dev.158485

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.2017

    • Author(s)
      Ebina-Shibuya R, Matsumoto M, Kuwahara M, Jang KJ, Sugai M, Ito Y, Funayama R, Nakayama K, Sato Y, Ishii N, Okamura Y, Kinoshita K, Kometani K, Kurosaki T, Muto A, Ichinose M, Yamashita M, Igarashi K.
    • Journal Title

      The Journal of biological chemistry

      Volume: 292 Issue: 44 Pages: 18098-18112

    • DOI

      10.1074/jbc.m117.808535

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 蛋白分解異常による新規筋萎縮性側索硬化症の発症機構2019

    • Author(s)
      渡辺 靖章, 中川 直, 鈴木 直輝, 割田 仁, 中山 啓子, 青木 正志
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 知的障害・自閉症関連因子SETD5によるrDNAのエピジェネティック制御2019

    • Author(s)
      中川 直, 中山 啓子
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Alternative Splicing of FBLN2 generates two proteins with different N-linked glycosylation patterns2019

    • Author(s)
      Wei,Chen Kao,Ryo Funayama, Keiko Nakayama
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ユビキチン化によるFACT複合体の機能制御2018

    • Author(s)
      中川直、諸星茜、中山啓子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸がんにおけるFibulin2スプライスバリアントの役割2018

    • Author(s)
      舟山亮、遠山慎吾、高唯真、中山啓子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mutation of cyclin F may contribute to Amyotrophic Lateral Sclerosis pathogensis by affecting VCP ATPase activity2018

    • Author(s)
      Yujao Yu, Akane Morohoshi, Tadashi Nakagawa, Keiko Nakayama
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科附属創生応用医学研究センターがん医学コアセンター細胞増殖制御分野

    • URL

      http://www.devgen.med.tohoku.ac.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科細胞増殖制御分野HP

    • URL

      http://www.devgen.med.tohoku.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科細胞増殖制御分野ホームページ

    • URL

      http://www.devgen.med.tohoku.ac.jp/index.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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