Regulation of helper/cytotoxic lineage choice by chromatin structures

• Project/Area Number: 26293109
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Taniuchi Ichiro 国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (20284573)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: T細胞分化 / 転写因子 / クロマチン / クロマチン構造 / 細胞分化 / 系列決定 / 免疫学 / 遺伝子発現制御 / CD4/CD8系列決定

Outline of Final Research Achievements

Helper versus cytotoxic lineage choice by T lymphocyte precursors serves as a good model to investigate how external environmental cue, TCR signals in this case, is integrated into genetic programming that govern cell fates. Since regulation of Thpok gene is a key to segregate these two fates, we examined how Thpok is regulated.
By using insertion ChIP, we found that cis-regulatory regions in the Thpok gene is assembled into the close proximity specifically in cytotoxic lineage. We also revealed that priming of Thpok gene by Bcl11b transcription factor, more specifically its C-terminal end Zinc-finger motif, during early thymocyte differentiation is essential for later coupling of TCR signals with appropriate Thpok expression. Lastly, our data unraveled that a genome organizer SATB1 plays essential roles in regulating expression of lineage specifying genes such as Thpok, Runx3 and Foxp3, to specify effect tor T cell subset.

Research Products

• [Int'l Joint Research] UCSF(米国)
• [Journal Article] Distinct requirement of Runx complexes for TCRβ enhancer activation at distinct developmental stages. (2017)
  • Author(s): Seo W, Muroi S, Akiyama K and Taniuchi I.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41351-41351
  • DOI: 10.1038/srep41351
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. (2017)
  • Author(s): Kitagawa Y, Ohkura N, Kidani Y, Vandenbon A, Hirota K, Kawakami R, Yasuda K, Motooka D, Nakamura S, Kondo M, Taniuchi I, Kohwi-Shigematsu T, Sakaguchi S.
  • Journal Title: Nat Immunol. Volume: 18(2) Issue: 2 Pages: 173-183
  • DOI: 10.1038/ni.3646
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Essential roles of SATB1 in specifying T lymphocyte subsets (2017)
  • Author(s): Kakugawa K, Kojo S, Tanaka H, Seo W, Endo T, Kitagawa Y, Muroi S, Teno M, Yasmin N, Kohwi Y, Sakaguchi S, Kowhi-Shigematsu, T and Taniuchi I.
  • Journal Title: Cell Reports Volume: 印刷中
  • NAID: 40021496454
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of hematopoiesis and immune responses by long noncoding (lnc) RNAs (2017)
  • Author(s): Seo.W and Taniuchi I.
  • Journal Title: International Immunology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Runx3 guards cytotoxic CD8+ effectors against Tfh deviation in acute viral infection (2017)
  • Author(s): Shan Q, Zeng Z, Xing S, Li F, Hartwig S, Gullicksrud J, Su Y, Kurup S, Badovinac N, Su Y, Martin M, Taniuchi I, Harty J, Peng W, Badvinac V and Xue H-H
  • Journal Title: Nature Immunology Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Views on helper/cytotoxic lineage choice from a bottom-up approach. (2016)
  • Author(s): Taniuchi I
  • Journal Title: Immunol Rev. Volume: 271 Issue: 1 Pages: 98-113
  • DOI: 10.1111/imr.12401
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Core Binding Factor β Plays a Critical Role During Chondrocyte Differentiation. (2016)
  • Author(s): Park NR, Lim KE, Han MS, Che X, Park CY, Kim JE, Taniuchi I, Bae SC, Choi JY
  • Journal Title: J Cell Physio Volume: 231 Issue: 1 Pages: 162-71
  • DOI: 10.1002/jcp.25068
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transcriptional regulation of early T-cell development in the thymus. (2016)
  • Author(s): Seo W, Taniuchi I
  • Journal Title: Eur J Immunol. Volume: 46 Issue: 3 Pages: 531-8
  • DOI: 10.1002/eji.201545821
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development. (2016)
  • Author(s): Jiang Q, Qin X, Kawane T, Komori H, Matsuo Y, Taniuchi I, Ito K, Izumi S, Komori T
  • Journal Title: J Bone Miner Res Volume: 印刷中 Issue: 7 Pages: 1391-1404
  • DOI: 10.1002/jbmr.2814
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ThPOK represses CXXC5, which induces methylation of histone H3 lysine 9 in Cd40lg promoter by association with SUV39H1: implications in repression of CD40L expression in CD8+ cytotoxic T cells. (2016)
  • Author(s): Tsuchiya Y, Naito T, Tenno M, Maruyama M, Koseki H, Taniuchi I, Naoe Y.
  • Journal Title: J Leukoc Biol. Volume: 印刷中 Issue: 2 Pages: 327-338
  • DOI: 10.1189/jlb.1a0915-396rr
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development (2015)
  • Author(s): Bingtao Hao, Abani Kanta Naik , Akiko Watanabe , Hirokazu Tanaka , Liang Chen , Hunter W Richards, Motonari Kondo, Ichiro Taniuchi, Yoshinori Kohwi, Terumi Kohwi-Shigematsu, Michael S Krangel
  • Journal Title: Journal of experimental medicine Volume: 212 Issue: 5 Pages: 809-824
  • DOI: 10.1084/jem.20142207
  • Peer Reviewed
• [Journal Article] Central role of core binding factor β2 in mucosa-associated lymphoid tissue organogenesis in mouse (2015)
  • Author(s): T. Nagatake, S. Fukuyama, S. Sato, H. Okura, M. Tachibana, I. Taniuchi, K. Ito, M. Shimojou, N. Matsumoto, H, Suzuki, J. Kunisawa, and H. Kiyono
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127460-e0127460
  • DOI: 10.1371/journal.pone.0127460
  • NAID: 120006987038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of a novel lymphoid population in the murine epidermis. (2015)
  • Author(s): Almeida FF, Tenno M, Brzostek J, Li JL, Allies G, Hoeffel G, See P, Ng LG, Fehling HJ, Gascoigne NR, Taniuchi I, Ginhoux F.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 12554-12554
  • DOI: 10.1038/srep12554
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MAZR and Runx factors synergistically repress ThPOK during CD8+ T cell lineage development. (2015)
  • Author(s): Sakaguchi S, Hainberger D, Tizian C, Tanaka H, Okuda T, Taniuchi I, Ellmeier W
  • Journal Title: Journal of Immunology Volume: 195 Issue: 6 Pages: 2879-2887
  • DOI: 10.4049/jimmunol.1500387
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel Cd8-cis-regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells. (2015)
  • Author(s): Sakaguchi S, Hombauer M, Hassan H, Tanaka H, Yasmin N, Naoe Y, Bilic I, Moser MA, Hainberger D, Mayer H, Seiser C, Bergthaler A, Taniuchi I, Ellmeier W.
  • Journal Title: J Leukoc Biol. Volume: 97 Issue: 4 Pages: 635-644
  • DOI: 10.1189/jlb.1hi1113-597rr
  • Peer Reviewed
• [Journal Article] Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element. (2015)
  • Author(s): Majumder K, Koues O, Chan E, Kyle K, Horowitz J, Yang-Iott K, Bassing C, Taniuchi I, Krangel M, Oltz E
  • Journal Title: J.Exp.Med. Volume: 212 Issue: 1 Pages: 107-20
  • DOI: 10.1084/jem.20141479
  • Peer Reviewed
• [Journal Article] Runx/Cbfb signaling regulates postnatal development of granular convoluted tubule in the mouse submandibular gland. (2015)
  • Author(s): Islam MN, Itoh S, Yanagita T, Sumiyoshi K, Hayano S, Kuremoto K, Kurosaka H, Honjo T, Kawanabe N, Kamioka H, Sakai T, Ishimaru N, Taniuchi I, Yamashiro T
  • Journal Title: Dev Dyn. Volume: 244(3) Issue: 3 Pages: 488-496
  • DOI: 10.1002/dvdy.24231
  • Peer Reviewed / Open Access
• [Journal Article] Cbfb regulates bone development by stabilizing Runx family proteins. (2015)
  • Author(s): Qin X, Jiang Q, Matsuo Y, Kawane T, Komori H, Moriishi T, Taniuchi I, Ito K, Kawai Y, Rokutanda S, Izumi S, Komori T.
  • Journal Title: Journal of bone and mineral research Volume: 30 Issue: 4 Pages: 706-714
  • DOI: 10.1002/jbmr.2379
  • Peer Reviewed
• [Journal Article] Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development. (2014)
  • Author(s): Mishima Y, Wang C, Miyagi S, Saraya A, Hosokawa H, Mochizuki-Kashio M, Nakajima-Takagi Y, Koide S, Negishi M, Sashida G, Naito T, Ishikura T, Onodera A, Nakayama T, Tenen DG, Yamaguchi N, Koseki H, Taniuchi I, Iwama A.
  • Journal Title: Nature Communications Volume: 18 Issue: 1 Pages: 5872-5882
  • DOI: 10.1038/ncomms6872
  • Peer Reviewed / Open Access
• [Journal Article] Cbfb deficiency results in differentiation blocks and stem/progenitor cell expansion in hematopoiesis. (2014)
  • Author(s): Wang CQ, Chin DW, Chooi JY, Wee Joo C, Taniuchi I, Tergaonkar V, Osato M.
  • Journal Title: Leukemia Volume: 29 Issue: 3 Pages: 753-7
  • DOI: 10.1038/leu.2014.316
  • Peer Reviewed / Open Access
• [Journal Article] The Role of BTB-Zinc Finger Transcription Factors During T Cell Development and in the Regulation of T Cell-mediated Immunity. (2014)
  • Author(s): Ellmeier W, Taniuchi I.
  • Journal Title: Curr Top Microbiol Immunol. Volume: 381 Pages: 21-49
  • DOI: 10.1007/82_2014_374
  • ISBN: 9783319073941, 9783319073958
• [Journal Article] Functional B-1 progenitor cells are present in the hematopoietic stem cell deficient embryo and depend on Cbfβ for their development. (2014)
  • Author(s): Kobayashi M, Shelly CW, Seo W, Vemula S, Liu Y, Taniuchi I and Yoshimoto M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111 Issue: 33 Pages: 12151-6
  • DOI: 10.1073/pnas.1407370111
  • Peer Reviewed / Open Access
• [Journal Article] Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia predisposition due to transcriptional and DNA repair defects. (2014)
  • Author(s): Wang CQ, Krishnan V, Tay LS, Chin DW, Koh CP, Chooi JY, Nah GS, Du L, Jacob B, Yamashita N, Lai SK, Tan TZ, Mori S, Taniuchi I, Tergaonkar V, Ito Y, Osato M.
  • Journal Title: Cell Reports Volume: 8 Pages: 767-82
  • Peer Reviewed / Open Access
• [Journal Article] CD4^+ T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2 (2014)
  • Author(s): Boucheron N, Tschismarov R, Goeschl L, Moser M.A, Lagger S, Sakaguchi S, Winter M, Lenz F, Vitko D, Breitwieser FP, Muller L, Hassan H, Bennett K.L, Colinge J, Schreiner W, Egawa T, Taniuchi I, Matthias P, Seiser C Ellmeier W
  • Journal Title: Nat. Immunol Volume: 15 Issue: 5 Pages: 439-448
  • DOI: 10.1038/ni.2864
  • Peer Reviewed / Open Access
• [Presentation] Runs 転写因子による獲得免疫系の発生制御機構 (2017)
  • Author(s): 谷内 一郎
  • Organizer: 122回 日本解剖学会
  • Place of Presentation: 長崎大学
  • Year and Date: 2017-03-28
  • Int'l Joint Research / Invited
• [Presentation] Transcriptional program that confer thymus homing capacity (2017)
  • Author(s): 谷内 一郎
  • Organizer: 第7回国際KTCC
  • Place of Presentation: 京都大学
  • Year and Date: 2017-03-13
  • Int'l Joint Research / Invited
• [Presentation] 胸腺内Tリンパ球分化機構 (2016)
  • Author(s): 谷内 一郎
  • Organizer: 26回 日本サイトメトリー学会
  • Place of Presentation: 九州大学
  • Year and Date: 2016-07-23
  • Invited
• [Presentation] Regulation of Langerhans cell development by Runx transcription factor complexes (2016)
  • Author(s): 谷内 一郎
  • Organizer: Immunological Diseases and Translational Research Forum 2016
  • Place of Presentation: Shanghai
  • Int'l Joint Research / Invited
• [Presentation] Repression of CCL5 by Runx/Cbfb is essential to prevent lung infiltration (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: RUNX 2015
  • Place of Presentation: Rehovot, Israel
  • Year and Date: 2015-10-18
  • Int'l Joint Research / Invited
• [Presentation] Linking environment cues with mechanisms that control specification of T lymphocyte lineages requires a proper positioning of regulatory regions (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: EMBO conference
  • Place of Presentation: Paris, France
  • Year and Date: 2015-09-29
  • Int'l Joint Research
• [Presentation] Roles of SATB1 during Thymocyte Development (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: FASEB Conference
  • Place of Presentation: Montana, USA
  • Year and Date: 2015-08-16
  • Int'l Joint Research / Invited
• [Presentation] T細胞分化研究: 核内からTCR信号をつなぐ道のり (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: 第17回免疫サマースクール2015,
  • Place of Presentation: 淡路国際会議場、日本
  • Year and Date: 2015-07-21
  • Invited
• [Presentation] Roles of SATB1 during thymocyte differentiation (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: KTCC2015
  • Place of Presentation: 京都, 日本
  • Year and Date: 2015-05-15
• [Presentation] Roles of Bcl11b during thymocyte differentiation (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: Venice Thymus Meeting
  • Place of Presentation: Venice, Italy
  • Year and Date: 2015-04-09
  • Int'l Joint Research
• [Presentation] Transcriptional Regulation of T Cell Development in the Thymus (2015)
  • Author(s): Ichiro Taniuchi
  • Organizer: Keystone Symposium
  • Place of Presentation: Snowbirds, USA
  • Year and Date: 2015-04-01
  • Int'l Joint Research / Invited
• [Presentation] Cell fate determination in the thymus (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: The 43rd Annual Meeting of Japanese Society of Immunology
  • Place of Presentation: 京都
  • Year and Date: 2014-12-11
  • Invited
• [Presentation] Road to become CD4 helper T cells (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: Seminar at Duke University Medical Center, Department of Immunology
  • Place of Presentation: Durham, NC, USA
  • Year and Date: 2014-11-13
  • Invited
• [Presentation] Road to become CD4 helper T Cells (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: Seminar at Washington University in St. Louis School of Medicine, Department of Pathology & Immunology
  • Place of Presentation: Saint Louis, MO, USA
  • Year and Date: 2014-11-11
  • Invited
• [Presentation] Transcriptional regulation of CD4/CD8 lineage choice: roles of Bcl11b and SATB1 (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: France-Japan Immunology meeting
  • Place of Presentation: Cassis, France
  • Year and Date: 2014-10-23
  • Invited
• [Presentation] Roles of Runx Transcription Factor Family During T Lymphocyte Development (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: SIgN Immunology Seminar
  • Place of Presentation: Singapore
  • Year and Date: 2014-08-28
  • Invited
• [Presentation] Transcriptional Control of Helper/Cytotoxic Lineage Choice in The Thymus (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: RIKEN IMS-JSI International Symposium on Immunology 2014
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-26
  • Invited
• [Presentation] Regulation of CD4 helper versus Cd8 cytotoxic lineage choice by transcription factors (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: AIM Series Seminar
  • Place of Presentation: Pohang, Korea
  • Year and Date: 2014-05-21
  • Invited
• [Presentation] Regulation of local chromatin loop at the Thpok in the CD4/CD8 lineage decision (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: The 24th Kyoto T Cell Conference (KTCC 2014)
  • Place of Presentation: 京都
  • Year and Date: 2014-05-16
• [Presentation] Transcriptional conotrol of helper/cytotoxic lineage choice in the thymus (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: AAI Immunology 2014
  • Place of Presentation: Pittsburgh, Pennsylvania, USA
  • Year and Date: 2014-05-05
  • Invited
• [Presentation] Regulation of local chromatin loop at the Thpok in the CD4/CD8 lineage decision by Bcl11b and SATB1 (2014)
  • Author(s): Ichiro Taniuchi
  • Organizer: Gene Expression & Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2014-04-23