Functional analysis of ATF2 gene family members by using knockout mouse

• Project/Area Number: 25460377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Maekawa Toshio 国立研究開発法人理化学研究所, 石井分子遺伝学研究室, 研究員 (90201764)
• Research Collaborator: Liu Binbin
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 転写因子 / ストレス / ATF7 / テロメア / 自然免疫 / マクロファージ / 長期記憶 / エピジェネティック / ATF-7 / Ku70/Ku80 / p38シグナル伝達経路 / TERT / 次世代への伝達 / p38シグナル経路 / テロメラーゼ / 炎症

Outline of Final Research Achievements

We studied the function of stress-response transcription factor ATF7 by using the ATF7 gene knockout mouse. At first, we found that ATF7 made complex with Ku70/Ku80 and telomerase and regulated telomere length. This function was found not only in mouse cells but also in human cells.
Second, we found that ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages. Treatment with lipopolysaccharide increased basal expression of target genes. And these increased expressions were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.

Research Products

• [Int'l Joint Research] Universite de Strasbourg(France)
• [Journal Article] In utero TNF-α treatment induces telomere shortening in young adult mice in an ATF7-dependent manner (2016)
  • Author(s): B. Liu, T Maekawa, B. Chatton, S. Ishii
  • Journal Title: FEBS Open Bio Volume: 6 Issue: 1 Pages: 56-63
  • DOI: 10.1002/2211-5463.12006
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. (2015)
  • Author(s): Yoshida K, Maekawa T, Zhu Y, Renard-Guillet C, Ishibashi K,Chatton B, Inoue K, Uchiyama T, Yamada T, Ohno N, Shirahige K, Okada-Hatakeyama M, Ishii S.
  • Journal Title: Nat Immunol. Volume: 16(10) Issue: 10 Pages: 1034-43
  • DOI: 10.1038/ni.3257
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory (2016)
  • Author(s): K. Yoshida, T. Maekawa, Y. Zhu, C. Renard-Guillet, B. Chatton, K. Inoue, T Uchiyama, K. Ishibashi, T. Yamada, N. Ohno, K. Shirahige, M. Okada-Hatakeyama, S. Ishii
  • Organizer: RIKEN Epigenetics International Symposium
  • Place of Presentation: 理研・鈴木梅太郎ホール、和光市、埼玉県
  • Year and Date: 2016-02-15
  • Int'l Joint Research
• [Presentation] ATF7 mediates stress-induced telomere shortening (2016)
  • Author(s): T. Maekawa, L. Binbin, K. Yoshida, S. Ishii
  • Organizer: RIKEN Epigenetics International Symposium
  • Place of Presentation: 理研・鈴木梅太郎ホール、和光市、埼玉県
  • Year and Date: 2016-02-15
  • Int'l Joint Research
• [Presentation] TNF-alpha treatment in fathers programs telomere shortening in mouse offspring (2015)
  • Author(s): Binbin Liu, Toshio Maekawa Shunsuke Ishii
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
• [Presentation] 転写因子ATF7を介したストレスによるテロメアの長さの制御 (2015)
  • Author(s): 前川利男、Binbin Liu、吉田圭介、仲村賢一、田久保海誉、増富健吉、小池学、石川冬木、石井俊輔
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
• [Presentation] ATF7はエピジェネティック記憶を通じて、自然免疫記憶を制御する (2015)
  • Author(s): 吉田圭介、前川利男、Yujuan Zhu、Claire R. Guillet、Bruno Chatton、井上健太郎、内山健、石橋健一、山田拓司、大野尚仁、白鬚克彦、岡田眞里子、石井俊輔
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
• [Presentation] 転写因子ATF-7を介したストレスによるテロメアの長さの制御 (2014)
  • Author(s): 前川 利男、Binbin Liu、吉田 圭介、仲村 賢一、田久保 海誉、石井 俊輔
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜市 パシフィコ横浜
  • Year and Date: 2014-11-26
• [Presentation] ストレスによるエピゲノム変化の遺伝
  • Author(s): 前川利男、石井俊輔
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 奈良市、新公会堂
  • Invited
• [Presentation] 転写因子ATF-7を介したストレスによる老化と次世代への遺伝
  • Author(s): 前川利男
  • Organizer: 理研シンポジウム
  • Place of Presentation: 茨城県つくば市、理研BRC
• [Presentation] 転写因子ATF-7を介したストレスによるテロメアの長さの制御
  • Author(s): 前川 利男、Binbin Liu、吉田 圭介、仲村 賢一、田久保 海誉、石井 俊輔
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸市、神戸ポートアイランド
• [Remarks] 理化学研究所・石井分子遺伝学研究室・ ホームページ
  • URL: http://rtcweb.rtc.riken.jp/lab/mg/mg.html
• [Remarks] 理化学研究所 研究紹介 石井分子遺伝学研究室
  • URL: http://www.riken.go.jp/research/labs/distinguished/mol_genet/