• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Coupring mechanism of methionine metabolism and epigenome

Planned Research

Project AreaCrosstalk of transcriptional control and energy pathways by hub metabolites
Project/Area Number 23116003
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

IGARASHI Kazuhiko  東北大学, 医学(系)研究科(研究院), 教授 (00250738)

Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥123,318,000 (Direct Cost: ¥94,860,000、Indirect Cost: ¥28,458,000)
Fiscal Year 2015: ¥21,099,000 (Direct Cost: ¥16,230,000、Indirect Cost: ¥4,869,000)
Fiscal Year 2014: ¥21,099,000 (Direct Cost: ¥16,230,000、Indirect Cost: ¥4,869,000)
Fiscal Year 2013: ¥26,130,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥6,030,000)
Fiscal Year 2012: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2011: ¥29,120,000 (Direct Cost: ¥22,400,000、Indirect Cost: ¥6,720,000)
Keywords発現制御 / 発生・分化 / プロテオーム / マイクロアレイ / 免疫学
Outline of Final Research Achievements

Regulation of epigenome relies on methylation of DNA and histones, which utilizes S-adenosyl-L-methoinine (SAM) as a sole methyl donor. SAM is synthesized by methionine adenosyltransferase (MAT) using methionine and ATP as substrates. In this research project, we discovered the molecular mechanism for the nuclear accumulation of MATII, one of the isozyme of MAT in higher eukaryotes. We also found that nuclear MATII interacted with various chromatin and transcription regulators, promoted histone H3 lysine 9 trimethylation of its target genes, and thus repress their expression. MATII also promoted formation of heterochromatin structure of certain chromatin subregions. These observations support our original contention that SAM is synthesized in nuclei for chromatin and gene expression (“local synthesis of SAM for local consumption” model). Next important step will be to understand how the activity of nuclear SAM is regulated during cell differentiation and/or proliferation.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (44 results)

All 2016 2015 2014 2013 2012 2011 Other

All Int'l Joint Research (1 results) Journal Article (17 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (20 results) (of which Int'l Joint Research: 1 results,  Invited: 10 results) Book (2 results) Remarks (4 results)

  • [Int'l Joint Research] Jawaharlal Nehru Center for ASR(インド)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes.2016

    • Author(s)
      Dhanasekaran, K., Kumari, S., Boopathi, R., Shima, H., Swaminathan, A., Bachu, M., Ranga, U., Igarashi, K., and Kundu, T.K.
    • Journal Title

      FEBS J.

      Volume: 283 Issue: 6 Pages: 968-985

    • DOI

      10.1111/febs.13653

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The transcription factor Bach2 is phosphorylated at multiple sites in murine B cells but a single site prevents its nuclear localization2016

    • Author(s)
      Ando R, Shima H, Tamahara T, Sato Y, Watanabe-Matsui M, Kato H, Sax N, Motohashi H, Taguchi K, Yamamoto M, Nio M, Maeda T, Ochiai K, Muto A, Igarashi K
    • Journal Title

      J Biol Chem

      Volume: 291 Issue: 4 Pages: 1826-1840

    • DOI

      10.1074/jbc.m115.661702

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3*2016

    • Author(s)
      Tanaka H
    • Journal Title

      JBC

      Volume: 291 Issue: 12 Pages: 6316-6330

    • DOI

      10.1074/jbc.m116.713842

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network.2014

    • Author(s)
      Igarashi K, Ochiai K, Itoh-Nakadai A, and Muto A.
    • Journal Title

      Immunol. Rev.

      Volume: 261 Issue: 1 Pages: 116-125

    • DOI

      10.1111/imr.12201

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The transcription repressors Bach2 and Bach1 promote B cell development by repressing myeloid program.2014

    • Author(s)
      Itoh-Nakadai A, Hikota R, Muto A, Kometani K, Matsui-Watanabe M, Sato Y, Kobayashi M, Nakamura A, Miura Y, Yano Y, Tashiro S, Sun J, Ikawa T, Ochiai K, Kurosaki T, and Igarashi K.
    • Journal Title

      Nature Immunol.

      Volume: 15 Issue: 12 Pages: 1171-1180

    • DOI

      10.1038/ni.3024

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages.2014

    • Author(s)
      Haldar, M., Kohyama, M., So, A.Y., Kc, W., Wu, X., Briseno, C.G., Satpathy, A.T., Kretzer, N.M., Arase, H., Rajasekaran, N.S., Wang, L., Egawa, T., Igarashi, K., Baltimore, D., Murphy, T.L., and Murphy, K.M.
    • Journal Title

      Cell

      Volume: 156 Issue: 6 Pages: 1223-1234

    • DOI

      10.1016/j.cell.2014.01.069

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between BACH2 expression and clinical prognosis in diffuse large B-cell lymphoma.2014

    • Author(s)
      Ichikawa, S., Fukuhara, N., Katsushima, H., Takahashi, T., Yamamoto, J., Yokoyama, H., Sasaki, O., Fukuhara, O., Nomura, J., Ishizawa, K., Ichinohasama, R., Muto, A., Igarashi, K., and Harigae, H.
    • Journal Title

      Cancer Science

      Volume: in press Issue: 4 Pages: 437-444

    • DOI

      10.1111/cas.12361

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hemopexin-dependent heme uptake via endocytosis regulates the Bach1 transcription repressor and heme oxygenase gene activation.2014

    • Author(s)
      Hada, H., Shiraki, T., Watanabe-Matsui, M., and Igarashi, K.
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: in press Issue: 7 Pages: 2351-2360

    • DOI

      10.1016/j.bbagen.2014.02.029

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.2013

    • Author(s)
      Kera, Y., Katoh, Y., Ohta, M., Matsumoto, M., Takano-Yamamoto, T. and Igarashi, K.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Issue: 19 Pages: 12592-13601

    • DOI

      10.1074/jbc.m112.429738

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis.2013

    • Author(s)
      Roychoudhuri, R., Hirahara, K., Mousavi, K., Clever, D., Klebanoff, C. A., Bonelli, M., Sciume, G., Zare, H., Vahedi, G., Dema, B., Yu, Z., Liu, H., Takahashi, H., Rao, M., Muranski, P., Crompton, J. G., Punkosdy, G., Muto, A., Igarashi, K., et al.
    • Journal Title

      Nature

      Volume: 498 Issue: 7455 Pages: 506-510

    • DOI

      10.1038/nature12199

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint.2013

    • Author(s)
      Swaminathan, S., Huang, C., Geng, H., Chen, Z., Harvey, R., Kang, H., Ng, C., Titz, B., Hurtz, C., Sadiyah, M. F., Nowak, D., Thoennissen, G. B., Rand, V., Graeber, T. G., Koeffler, H. P., Carrooll, W. L. Willman, C. L., Hall, A. G., Igarashi, K., Melnick, A. and Muschen, M.
    • Journal Title

      Nature Medicine

      Volume: 19 Issue: 8 Pages: 1014-1022

    • DOI

      10.1038/nm.3247

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bach2 maintains T cells in a naive state by suppressing effector memory-related genes2013

    • Author(s)
      Tsukumo, S., Unno, M., Muto, A., Takeuchi, A., Kometani, K., Kurosaki, T., Igarashi, K., Saito, T
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 110 Issue: 26 Pages: 10735-40

    • DOI

      10.1073/pnas.1306691110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-&βinduces transcription factors MafK and Bach1 to suppress expression of the heme oxygenase-1 gene.2013

    • Author(s)
      Okita Y, Kamoshida A, Suzuki H, Itoh K, Motohashi H, Igarashi K, Ogami T, Koinuma D, Kato M.
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 28 Pages: 20658-20667

    • DOI

      10.1074/jbc.m113.450478

    • NAID

      120007136878

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function2013

    • Author(s)
      Nakamura A, Ebina-Shibuya R, Itoh-Nakadai A, Muto A, Shima H, Saigusa D, Aoki J, Ebina M, Nukiwa T, Igarashi K.
    • Journal Title

      J Exp Med.

      Volume: 210 Issue: 11 Pages: 2191

    • DOI

      10.1084/jem.20130028

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage2013

    • Author(s)
      Shima H, Suzuki H, Sun J, Kono K, Shi L, Kinomura A, Horikoshi Y, Ikura T, Ikura M, Kanaar R, Igarashi K, Saitoh H, Kurumizaka H, Tashiro S
    • Journal Title

      J Cell Sci

      Volume: 126 Pages: 5284-5292

    • DOI

      10.1242/jcs.133744

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.2013

    • Author(s)
      Kera Y, Katoh Y, Ohta M, Matsumoto M, Takano-Yamamoto T, Igarashi K.
    • Journal Title

      J Biol Chem

      Volume: in press

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bach1 is critical for the transformation of mouse embryonic fibroblast by RasV12 and maintains ERK signaling2012

    • Author(s)
      Nakanome A, Brydoun A, Matsumoto M, Ota K, Funayama R, Nakayama K, Ono M, Shiga K, Kobayashi T, Igarashi K
    • Journal Title

      Oncogene

      Volume: 32 Issue: 27 Pages: 3231-3245

    • DOI

      10.1038/onc.2012.336

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] local synthesis of S-adenosylmethionine for local consumption, version 2: methylation of chromatin and beyond.2016

    • Author(s)
      五十嵐和彦
    • Organizer
      転写代謝システム国際シンポジウム
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Local production of S-adenosylmethionine for local consumption to promote and to regulate methylation of chromatin and beyond.2015

    • Author(s)
      五十嵐和彦
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会合同大会)
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] S-アデノシルメチオニン合成酵素MAT2Aの発現は3' UTRアデニンメチル化が介するmRNA安定性により制御される2015

    • Author(s)
      島弘季
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会合同大会)
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] S-アデノシルメチオニンの核内産生機構とそのエピゲノム制御における役割2015

    • Author(s)
      五十嵐和彦
    • Organizer
      第26回フォーラム・イン・ドージン
    • Place of Presentation
      熊本ホテルキャッスル(熊本県熊本市)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] S-アデノシルメチオニン合成酵素のクロマチンRNA制御における機能と肝再生におけるクロマチン転写ネットワーク2015

    • Author(s)
      五十嵐和彦
    • Organizer
      長崎医学会特別講演
    • Place of Presentation
      長崎大学大学院医歯薬学総合研究科(長崎県長崎市)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] SAM合成酵素MAT2A mRNA量はメチル-6-アデノシン修飾を介して制御される2015

    • Author(s)
      島弘季
    • Organizer
      転写代謝システム会議2015 at 熊本
    • Place of Presentation
      菊南温泉ユウベルホテル(熊本県熊本市)
    • Year and Date
      2015-06-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program.2015

    • Author(s)
      A Ito-Nakadai, A Muto, M Watanabe-Matsui, K Kometani, Y Sato, T Ikawa, K Ochiai, T Kurosaki, K Igarashi
    • Organizer
      2015 Keystone Symposia Conference : The Golden Anniversary of B Cell Discovery
    • Place of Presentation
      Fairmont Banff Springs (カナダ、バンフ)
    • Year and Date
      2015-03-22 – 2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Local synthesis of S-adenosylmethionine for local consumption: how metabolism is coupled with epigenomic regulation.2015

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      5th Meeting of the Asian Forum of Chromosome and Chromatin Biology
    • Place of Presentation
      Jawaharlal Nehru Center for Advanced Scientific Research (インド、バンガロール)
    • Year and Date
      2015-01-15 – 2015-01-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Contribution of nuclear localized MATIIα to nuclear SAM pool.2015

    • Author(s)
      Masayuki Ebina, Yasutake Katoh, Kazuhiko Igarashi
    • Organizer
      5th Meeting of the Asian Forum of Chromosome and Chromatin Biology
    • Place of Presentation
      Jawaharlal Nehru Center for Advanced Scientific Research (インド、バンガロール)
    • Year and Date
      2015-01-15 – 2015-01-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] The function of methionine adenosyltransferase 2 in plasma cell differentiation.2014

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      第37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
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] SAM合成酵素の核内局在によるエピゲノムの制御2014

    • Author(s)
      五十嵐和彦
    • Organizer
      第二回がんと代謝研究会
    • Place of Presentation
      東京理科大学葛飾キャンパス(東京都葛飾区)
    • Year and Date
      2014-07-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Nuclear localization of methionine adenosyltransferase II and its function in B cell response.2014

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      17th Chromatin Assembly Meeting
    • Place of Presentation
      Bangalore, India
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of B cell activation and differentiation by methionine adenosyltransferase II.2013

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      International Symposium on Transcription and Metabolism
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 転写因子―エピゲノムネットワークによる遺伝情報のプログラミング2013

    • Author(s)
      五十嵐和彦
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      江陽グランドホテル(宮城県仙台市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Heme as a signaling molecule for globin gene regulation and iron homeostasis.2013

    • Author(s)
      M.Kobayashi., H.Hada., A.Muto.,H.Harigae. K.Igarashi.
    • Organizer
      Cold Spring Harbor Laboratory Meeting Metabolic Sgnaling & Disease:From Cell to Ofganism
    • Place of Presentation
      Cold Spring Harbor Laboratory, U.S.A.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Coupling of metabolism and transcription by a denosylmethionine transferase2011

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      Invited Seminar, Jawaharlal Nehru Center for Advanced Scientific Research, India
    • Place of Presentation
      Bangalore、インド
    • Year and Date
      2011-12-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coupling of metabolism and transcription by adenosylmethionine transferase2011

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      Invited Seminar, Institute of Chemical Biology, India
    • Place of Presentation
      Kolkata、インド
    • Year and Date
      2011-12-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] MafK-dependent and -independent nuclear function of methionine adenosyltransferase2011

    • Author(s)
      Kazuhiko Igarashi
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] SAMIT核内モジュールによるSAM合成とヒストンメチル化の共役2011

    • Author(s)
      五十嵐和彦
    • Organizer
      日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 転写因子によるB細胞-形質細胞分化調節ネットワーク

    • Author(s)
      五十嵐和彦、落合恭子、加藤恭丈、武藤哲彦
    • Organizer
      国際高等研究所クロマチンデコーディング集会
    • Place of Presentation
      国際高等研究所
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] Epigenetics:Dvelopment and Disease2012

    • Author(s)
      Igarashi K, Katoh Y.
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Book] Epigenetics : Development and Disease2012

    • Author(s)
      Kazuhiko Igarashi, et al
    • Publisher
      Springer
    • Related Report
      2011 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科生物化学分野ホームページ

    • URL

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

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科生物化学分野ホームページ

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks] 研究室HP

    • URL

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

    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究室HP

    • URL

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

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-08-01   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi