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Shared mechanisms of the transcription factor IRF8 and the cAMP pathway in macrophage differentiation

Research Project

Project/Area Number 23590343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionYokohama City University

Principal Investigator

NISHIYAMA Akira  横浜市立大学, 医学(系)研究科(研究院), 准教授 (80589664)

Co-Investigator(Renkei-kenkyūsha) TAMURA Tomohiko  横浜市立大学, 医学研究科, 教授 (50285144)
ICHINO Motohide  横浜市立大学, 医学部, 助教 (60271368)
HOTTA Chie  横浜市立大学, 医学部, 助教 (80363810)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細胞内シグナル伝達 / 血球分化 / 転写因子 / 遺伝子発現 / 網羅的解析 / 免疫学 / マイクロアレイ / シグナル伝達
Research Abstract

Cell differentiation requires appropriate changes in gene expression patterns, which are tightly regulated by cell type-specific transcription factors. Dysregulation of these processes can result in disorders incuding leukemias. IRF8 is a hematopoietic transcription factor that regulates the development of multiple immune cell types, and also it is considered as an important regulatory factor for chronic myelogenous leukemia. In this study, we have investigated the differentiation program of myeloid cells by functional analyses of IRF8 with the aim of the future clinical application for chronic myelogenous leukemia. We performed gene expression profiling of macrophage differentiation induced by multiple procedures including IRF8 ectopic expression. We found the common transcription factors in macrophage differentiation induced by multiple procedures. Indeed, the ectopic expression of these transcription factors induced macrophage differentiation without IRF8 expression.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (48 results)

All 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (33 results) (of which Invited: 1 results) Remarks (4 results)

  • [Journal Article] The transcription factor IRF8 counteracts BCR-ABL to rescue dendritic cell development in chronic myelogenous leukemia.2013

    • Author(s)
      Watanabe T, Hotta C, Koizumi S, Miyashita K, Nakabayashi J, Kurotaki D, Sato GR, Yamamoto M, Nakazawa M, Fujita H, Sakai R, Fujisawa S, Nishiyama A, Ikezawa Z, Aihara M, Ishigatsubo Y, Tamura T.
    • Journal Title

      Cancerresearch

      Volume: 73(22) Issue: 22 Pages: 6642-53

    • DOI

      10.1158/0008-5472.can-13-0802

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] WHSC1 links transcription elongation to HIRA-mediated histone H3.3 deposition in activated genes.2013

    • Author(s)
      Sarai N., Nimura K., Tamura T., Kanno T., Patel M.C., Heightman T. D., Ura K. and Ozata K.
    • Journal Title

      EMBO J

      Volume: 32 Issue: 17 Pages: 2392-2406

    • DOI

      10.1038/emboj.2013.176

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] BRD4 coordinates recruitment of pause-release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon stimulated genes2013

    • Author(s)
      Patel MC, Tamura T(他7人)
    • Journal Title

      Mol Cell Biol

      Volume: 33 Issue: 12 Pages: 2497-2507

    • DOI

      10.1128/mcb.01180-12

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells2013

    • Author(s)
      Iwasaki, Y.
    • Journal Title

      Eur J Immunol

      Volume: undefined Issue: 4 Pages: 1063-73

    • DOI

      10.1002/eji.201242942

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of the IRF8-KLF4 transcription factor cascade in murine monocyte differentiation.2013

    • Author(s)
      Daisuke Kurotaki et al.
    • Journal Title

      Blood

      Volume: 121 Issue: 10 Pages: 1839-1849

    • DOI

      10.1182/blood-2012-06-437863

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells2013

    • Author(s)
      Akira Nishiyama et al.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1 Pages: 1390-1390

    • DOI

      10.1038/srep01390

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of JNK triggers release of Brd4 from mitotic chromosomes and mediates protection from drug-induced mitotic stress.2012

    • Author(s)
      Akira Nishiyama et al.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 5 Pages: e34719-e34719

    • DOI

      10.1371/journal.pone.0034719

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of JNK triggers release of Brd4 from mitotic chromosomes and mediates protection from drug-induced mitotic stress.2012

    • Author(s)
      Nishiyama, A., Dey, A., Tamura, T., Ko, M., and Ozato, K.
    • Journal Title

      10.1371/journal.pone.0034719

      Volume: 7

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of mouse ES cell lines engineered for the forced induction of transcription factors2011

    • Author(s)
      Correa-Cerro LS, Nishiyama A(他17人)
    • Journal Title

      Scientific Rep

      Volume: 1 Issue: 1 Pages: 167-167

    • DOI

      10.1038/srep00167

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development2011

    • Author(s)
      Yamamoto M, et al
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 10 Pages: e25812-e25812

    • DOI

      10.1371/journal.pone.0025812

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity2011

    • Author(s)
      Sharov AA, Nishiyama A(他6人)
    • Journal Title

      BMC Genomics

      Volume: 12 Issue: 1 Pages: 102-102

    • DOI

      10.1186/1471-2164-12-102

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] IRF8 Inhibits the Activity of C/EBPαto Restrain Monocyte-Dendritic Cell Progenitors from Differentiating into Neutrophils2013

    • Author(s)
      Nishiyama A, Ichino M, Tamura T, et al
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2013-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] A dynamic and long-range chromatin control of Klf4 transcription by IRF8 in monocyte differentiation2013

    • Author(s)
      Nishiyama A, Tamura T, et al
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2013-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 単球分化において転写因子IRF8がKlf4プロモーターと遠位エンハンサーの長距離間の相互活性化を誘導する2013

    • Author(s)
      西山晃, 田村智彦, ら
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] A dynamic and long-range chromatin control of Klf4 transcription by IRF8 in monocyte differentiation2013

    • Author(s)
      Nishiyama A, Tamura T, et al
    • Organizer
      12th Human Proteome Organization World Congress
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-09-16
    • Related Report
      2013 Final Research Report
  • [Presentation] M期での転写メモリーとストレス応答におけるBRD4の役割2013

    • Author(s)
      西山晃, 田村智彦, ら
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] ゲノム規模解析による単球分化に重要なIRF8-KLF4転写因子カスケードの発見2012

    • Author(s)
      黒滝大翼, 西山晃, 田村智彦, ら
    • Organizer
      第35回分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Genome-wide analyses revealed the IRF8-KLF4 transcription factor cascade during monocyte differentiation2012

    • Author(s)
      Kurotaki D, Nishiyama A, Tamura T, et al
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2012-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Activation of JNK mediates protection from drug-induced mitotic stress by triggering release of Brd4 from mitotic chromosome2011

    • Author(s)
      Nishiyama A, Tamura T, et al
    • Organizer
      第34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)
    • Year and Date
      2011-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of the development of monocyte subsets by interferon regulatory factor 82011

    • Author(s)
      Kurotaki D, Ichino M, Nishiyama A, Tamura T, et al
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2011-11-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Selective regulation of monocyte subsets by the transcription factor Interferon Regulatory Factor 82011

    • Author(s)
      Kurotaki D, Ichino M, Nishiyama A, Tamura T, et al
    • Organizer
      9th Joint Meeting of the International Society for Interferon and Cytokine Research and the International Cytokine Society
    • Place of Presentation
      Firenze Fiera Congress and Exhibition Center(フィレンツェ,イタリア)
    • Year and Date
      2011-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] マラリアにおける樹状細胞分化の異常と転写因子IRFファミリー2011

    • Author(s)
      市野素英, 堀田千絵, 田村智彦
    • Organizer
      第80回日本寄生虫学会
    • Place of Presentation
      東京慈恵会医科大学(東京都)
    • Year and Date
      2011-07-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Selective regulation of monocyte subsets by the transcription factor Interferon Regulatory Factor 8.2011

    • Author(s)
      Kurotaki D, Ichino M, Nishiyama A, Sato G, Yamamoto M, Ozato K, Tamura T
    • Organizer
      9th Joint Meeting of the International Society for Interferon and Cytokine Research (ISICR) and the International Cytokine Society (ICS)
    • Place of Presentation
      Florence, Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] ミエロイド細胞の分化・機能制御におけるIRF4, IRF8の役割.2011

    • Author(s)
      山本道雄,加藤隆幸,堀田千絵,西山晃,黒滝大翼,吉成正裕,高見正道,市野素英,中澤正年,松山俊文,上條竜太郎,北川誠一,Keiko Ozato,田村智彦
    • Organizer
      第13回神奈川血液・免疫フォーラム
    • Place of Presentation
      小田急ホテルセンチュリー相模大野(神奈川県)
    • Related Report
      2011 Research-status Report
  • [Presentation] Regulation of the development of monocyte subsets by interferon regulatory factor 82011

    • Author(s)
      Kurotaki D, Ichino M, Nishiyama A, Sato G, Yamamoto M, Ozato K, Tamura T
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Research-status Report
  • [Presentation] IRF8 physically interacts with C/EBPα to inhibit the generation of granulocyte-macrophage progenitors and neutrophils.2011

    • Author(s)
      Tamura T, Yamamoto M, Osato N, Kurotaki D, Uno K, Nakazawa M, Nishiyama A, Ozato K
    • Organizer
      第34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)
    • Related Report
      2011 Research-status Report
  • [Presentation] The transcription factor IRF8 rescues the dendritic cell development impaired by p210 Bcr/Abl.2011

    • Author(s)
      Watanabe T, Hotta C, Sato GR, Yamamoto M, Fujita H, Sakai R, Fujisawa S, Nishiyama A, Aihara M, Ishigatsubo Y, Tamura T
    • Organizer
      第34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)
    • Related Report
      2011 Research-status Report
  • [Presentation] Activation of JNK mediates protection from drug-induced mitotic stress by triggering release of Brd4 from mitotic chromosome.2011

    • Author(s)
      Nishiyama A, Dey A, Tamura T, Ozato K
    • Organizer
      第34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)
    • Related Report
      2011 Research-status Report
  • [Presentation] The IRF8-KLF4 transcription factor cascade critically regulates the development of inflammatory monocytes

    • Author(s)
      Kurotaki D., Osato N., Nishiyama A., Yamamoto M., Ban T., Sato H., Nakabayashi J., Umehara M., Nakazawa M., Miyake N., Matsumoto N., Ozato K., Tamura T.
    • Organizer
      The Joint International Meeting of the Japanese Society for Interferon and Cytokine Research and Macrophage Molecular and Cellular Biology 2013
    • Place of Presentation
      都市センターホテル(東京都)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 転写因子IRF8は単球-樹状細胞前駆細胞においてC/EBPαの機能を阻害し、好中球分化能の喪失をもたらす

    • Author(s)
      黒滝大翼,山本道雄,宇野和宏,西山 晃,中林 潤,中澤正年,Herbert C. Morse III,Keiko Ozato,田村智彦
    • Organizer
      第24回日本生体防御学会学術総会
    • Place of Presentation
      くまもと森都心プラザ(熊本県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] A dynamic and long-range chromatin control of Klf4 transcription by IRF8 in monocyte differentiation.

    • Author(s)
      Nishiyama A, Kurotaki D, Tamura T.
    • Organizer
      12th Human Proteome Organization World Congress
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] M期での転写メモリーとストレス応答におけるBRD4の役割

    • Author(s)
      西山 晃,田村智彦,Kieko Ozato
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The transcription factor IRF8 overrides BCR-ABL to rescue dendritic cell development in chronic myeloid leukemia.

    • Author(s)
      Watanabe T., Hotta C., Koizumi S., Miyashita K., Nakabayashi J., Kurotaki D., Sato R. G., Yamamoto M., Nishiyama A., Aihara M., Ishigatsubo Y., Tamura T.
    • Organizer
      2013 Inaugural Meeting of the International Cytokine and Interferon Society
    • Place of Presentation
      Hyatt Regency San Francisco(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The IRF8-KLF4 transcription factor cascade is essential for the development of monocytes

    • Author(s)
      Kurotaki D., Osato N., Nishiyama A., Yamamoto M., Ban T., Sato H., Nakabayashi J., Umehara M., Nakazawa M., Miyake N., Matsumoto N., Ozato K., Tamura T.
    • Organizer
      2013 Inaugural Meeting of the International Cytokine and Interferon Society
    • Place of Presentation
      Hyatt Regency San Francisco(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] IRF8 inhibits the activity of C/EBPs to restrain neutrophil development in monocyte-DC progenitors.

    • Author(s)
      Kurotaki D., Yamamoto M., Uno K., Nishiyama A., Nakabayashi J., Morse H.C. 3rd., Ozato K., Tamura T.
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 単球分化において転写因子IRF8がKlf4プロモーターと遠位エンハンサーの長距離間の相互活性化を誘導する

    • Author(s)
      西山 晃,黒滝大翼,田村智彦
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] IRF8 inhibits the activity of C/EBP to restrain the neutrophil differentiation program in monocyte-dendritic cell progenitors.

    • Author(s)
      Kurotaki D., Yamamoto M., Nishiyama A., Uno K., Ichino M., Sasaki H., Ban T., Yoshinari M., Nakazawa M., Ozato K., Tamura T.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] IRF8 restrains monocyte-dendritic cell progenitors from differentiating into neutrophils by inhibiting C/EBP activity

    • Author(s)
      Kurotaki D., Yamamoto M., Nishiyama A., Uno K., Sasaki H., Ozato K., Tamura T.
    • Organizer
      55th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Ernest N. Morial Convention Center(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The transcription factor IRF8 is a key transcription factor for basophil development

    • Author(s)
      Kurotaki D., Sasaki H., Osato N., Sasaki I., Kaneda C., Sato H., Nishiyama A., Kaisho T., Aburatani H., Morse H.C. 3rd., Ozato K., Tamura T.
    • Organizer
      55th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Ernest N. Morial Convention Center(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] IRF8 Inhibits the Activity of C/EBP to Restrain Monocyte-Dendritic Cell Progenitors from Differentiating into Neutrophils

    • Author(s)
      Yamamoto M., Kurotaki D., Nishiyama A., Uno K., Ichino M., Nakazawa M., Ozato K., Tamura T.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] A dynamic and long-range chromatin control of Klf4 transcription by IRF8 in monocyte differentiation

    • Author(s)
      Nishiyama A., Kurotaki D., Tamura T.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome-wide analyses revealed the IRF8-KLF4 transcription factor cascade during monocyte differentiation

    • Author(s)
      Daisuke Kurotaki et al.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Impaired dendritic cell development in chronic myelogenous leukemia can be rescued by restoring expression of the transcription factor IRF8.

    • Author(s)
      Tomoya Watanabe et al.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ゲノム規模解析による単球分化に重要なIRF8-KLF4転写因子カスケードの発見

    • Author(s)
      黒滝大翼、他
    • Organizer
      第35回分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www-user.yokohama-cu.ac.jp/~immunol/

    • Related Report
      2013 Final Research Report
  • [Remarks] 横浜市立大学大学院医学研究科 免疫学教室

    • URL

      http://www-user.yokohama-cu.ac.jp/~immunol/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 横浜市立大学医学部 免疫学教室

    • URL

      http://www-user.yokohama-cu.ac.jp/~immunol

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www-user.yokohama-cu.ac.jp/~immunol/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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