Analysis of brain functions regulated by histone modification and development of psychiatric disorder animal models

• Project/Area Number: 25290031
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kyoto University (2014-2015); Kanazawa University (2013)
• Principal Investigator: Asano Masahide 京都大学, 医学(系)研究科(研究院), 教授 (50251450)
• Co-Investigator(Kenkyū-buntansha): NARUSE Chie 京都大学, 大学院医学研究科, 助教 (30372486) ; YOSHIHARA Toru 京都大学, 大学院医学研究科, 特定助教 (00401935)
• Co-Investigator(Renkei-kenkyūsha): SUGIHARA Kazushi 京都大学, 大学院医学研究科, 技術職員 (10377418)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: エピジェネティクス / 脳神経疾患 / 行動学 / 遺伝子改変マウス / 脳・神経 / 遺伝子組換えマウス

Outline of Final Research Achievements

To elucidate the function of histone modification factors including HP1γ in the brain, we generated nervous system-specific HP1γ-deficient mice. When the mice were applied to test-battery behavioral analysis, they showed marked low activity in the open-field and light-dark transition test. However, antidepressant and antianxiety drugs could not recover their low activity.
HP1γ-deficient neural stem cells (NSCs) isolated from the mice were tended to differentiate and adhere culture dishes after several passages. When gene expression levels were compared between HP1γ-deficient and wild-type NSCs, expression levels of several genes related to nervous system were significantly enhanced in HP1γ-deficient NSCs and the accumulation of repressive histone marks was reduced in these genes. These results suggest that HP1γ regulates gene expression through histone modifications.

Research Products

• [Journal Article] Interaction of BARD1 and HP1 Is Required for BRCA1 Retention at Sites of DNA Damage. (2015)
  • Author(s): Wu W, Nishikawa H, Fukuda T, Vittal V, Asano M, Miyoshi Y, Klevit RE, Ohta T
  • Journal Title: Cancer Res Volume: 75 Issue: 7 Pages: 1311-1321
  • DOI: 10.1158/0008-5472.can-14-2796
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] HP-1γ controls high-affinity antibody response to T-dependent antigens (2014)
  • Author(s): Ha, N., Pham, D-H., Naruse, C., Asano, M., and Thai, T-H.
  • Journal Title: Frontiers in Immunology Volume: 5 Pages: 271-271
  • DOI: 10.3389/fimmu.2014.00271
  • Peer Reviewed / Open Access
• [Journal Article] Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease. (2014)
  • Author(s): Lopatina, O., Yoshihara, T., Nishimura, T., Asano, M., Higashida, H., et al.
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 印刷中
  • NAID: 120007185667
  • Peer Reviewed
• [Journal Article] Displays of paternal mouse pup retrieval following communicative interaction with maternal mates (2013)
  • Author(s): Liu, H-X., Lopatina, O., Higashida, C., Fujimoto, H., Akther, S., Inzhutova, A., Liang, M., Zhong, J., Tsuji, T., Yoshihara, T., Sumi, K., Ishiyama, M., Ma, W-J., Ozaki, M., Yagitani, S., Yokoyama, S., Mukaida, N., Sakurai, T., Hori, O., Yoshioka, K., Hirao, A., Kato, Y., Ishihara, K., Kato, I., Okamoto, H., Cherepanov, S.M., Salmina, A.B., Hirai, H., Asano, M., Brown, D.A., Nagano, I., and Higashida, H.
  • Journal Title: Nat. Commun Volume: 4 Issue: 1 Pages: 1346-1346
  • DOI: 10.1038/ncomms2336
  • Peer Reviewed
• [Journal Article] A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells (2013)
  • Author(s): Ohno R, Nakayama M, Naruse C, Okashita N, Takano O, Tachibana M, Asano M, Saitou M, Seki Y
  • Journal Title: Development Volume: 140 Issue: 14 Pages: 2892-2903
  • DOI: 10.1242/dev.093229
  • Peer Reviewed
• [Presentation] マウス体軸形成に対するKdm6ファミリーの機能 (2015)
  • Author(s): 成瀬智恵，柴田進和，阿部可奈恵，川口隆之，杉原一司，伊川正人，浅野雅秀
  • Organizer: 第38回日本分子生物学会年会
  • 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
• [Presentation] マウス体軸形成に対するKdm6ファミリーの関与 (2015)
  • Author(s): 成瀬智恵，柴田進和，阿部可奈恵，川口隆之，杉原一司，伊川正人，浅野雅秀
  • Organizer: 第62回日本実験動物学会
  • Place of Presentation: 京都テルサ（京都府・京都市）
  • Year and Date: 2015-05-28
• [Presentation] Loss of HP1gamma affected the character of neural stem cells in culture (2014)
  • Author(s): Sakanishi, K., Abe, K., Yoshihara, T., Chie Naruse, C., Asano, M.
  • 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
• [Presentation] 胎盤特異的インプリンティング遺伝子におけるJmjd3の機能解析
  • Author(s): 川口隆之，成瀬智恵，柴田進和，浅野雅秀
  • Organizer: 第60回日本実験動物学会
  • Place of Presentation: つくば国際会議場（茨城県つくば市）
• [Remarks] 京都大学医学研究科附属動物実験施設 研究室 Research Unit
  • URL: http://www.anim.med.kyoto-u.ac.jp/research.htm
• [Remarks] 京都大学医学研究科実験動物学
  • URL: http://www.anim.med.kyoto-u.ac.jp/research.htm
• [Remarks] 学際科学実験センター遺伝子改変動物分野
  • URL: http://asrc.w3.kanazawa-u.ac.jp/