Epigenetic marking by histone variant H3.3 during myeloid cell differentiation

• Project/Area Number: 23659492
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Yokohama City University
• Principal Investigator: TAMURA Tomohiko 横浜市立大学, 医学研究科, 教授 (50285144)
• Co-Investigator(Kenkyū-buntansha): ADACHI Noritaka 横浜市立大学, 生命ナノシステム科学研究科, 教授 (30264675)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Akira 横浜市立大学, 医学研究科, 准教授 (80589664)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エピジェネティックメモリー / ヒストンH3.3 / 細胞分化 / マクロファージ / 網羅的解析 / 国際情報交流 / 米国 / 転写

Research Abstract

Cell differentiation in multicellular organisms is achieved by dynamic changes in gene expression pattern. Dysregulation of such processes can cause various diseases including cancers. Histone variant H3.3 plays an important role in epigenetic memory of active genes. In this study we mapped genome-wide distribution of H3.3 during macrophage differentiation. The results indicated that H3.3 may regulate several steps of transcription including elongation. We also identified H3.3K36 as an amino acid residue required for H3.3 incorporation into chromatin.

Research Products

• [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells (2013)
  • Author(s): Iwasaki, Y.
  • Journal Title: Eur J Immunol Volume: undefined Issue: 4 Pages: 1063-73
  • DOI: 10.1002/eji.201242942
  • 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
  • Peer Reviewed
• [Journal Article] IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. (2012)
  • Author(s): T. Masuda*, M. Tsuda*, R. Yoshinaga, H.Tozaki-Saitoh, K. Ozato, T. Tamura, K. Inoue.
  • Journal Title: Cell Rep. Volume: 1(4) Issue: 4 Pages: 334-40
  • DOI: 10.1016/j.celrep.2012.02.014
  • 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
  • Peer Reviewed
• [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development (2011)
  • Author(s): Yamamoto M, et al
  • Journal Title: PLoS ONE Volume: 6 Issue: 10 Pages: e25812-e25812
  • DOI: 10.1371/journal.pone.0025812
  • Peer Reviewed
• [Presentation] Activation of JNK mediates protection from drug-induced mitotic stress by triggering release of Brd4 from mitotic chromosome (2012)
  • 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)
  • Year and Date: 2012-12-15
• [Presentation] IRF8 physically interacts with C/EBPα to inhibit the generation of granulocyte-macrophage progenitors and neutrophils (2012)
  • 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)
  • Year and Date: 2012-12-15
• [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,大里直樹,西山 晃,山本道雄,佐藤英明,中林 潤,藩 龍馬,梅原茉里奈,三宅紀子,松本直通,中沢正年,Keiko Ozato,田村智彦
  • 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
• [Presentation] Impaired dendritic cell development in chronic myelogenous leukemia can be rescued by restoring expression of the transcription factor IRF8 (2012)
  • Author(s): Watanabe T, Hotta C, Kurotaki D, Sato RG, Yamamoto M, Nishiyama A, Tamura T
  • 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: 2012-12-07
• [Presentation] Genome-wide analyses revealed the IRF8-KLF4 transcription factor cascade during monocyte differentiation (2012)
  • Author(s): Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Sato H, Nakabayashi J, Ban T, Ozato K, Tamura T
  • 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
• [Presentation] ゲノム規模解析による転写因子 IRF8 を核とした単球分化制御プログラムの理解 (2012)
  • Author(s): 田村智彦
  • Organizer: 文部科学省イノベーションシステム整備事業 先端融合領域イノベーション創出拠点形成プログラム「翻訳後修飾プロテオミクス医療研究拠点の形成」第4回公開シンポジウム
  • Place of Presentation: 横浜情報文化センター(神奈川県)
  • Year and Date: 2012-10-01
• [Presentation] The transcription factor IRF8 in the pathogenesis and therapy of chronic myelogenous leukemia (2012)
  • Author(s): Tamura T
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌 (北海道)
  • Year and Date: 2012-09-21
• [Presentation] Chromatin exchange in interferon induced transcription (2012)
  • Author(s): Ozato K, Sarai N, Patel M, Debrosse M, Heightman T, Tamura T, Ura K
  • Organizer: 10th Joint Meeting of International Cytokine Society and International Society for Interferon and Cytokine Research
  • Place of Presentation: ジュネーブ、スイス
  • Year and Date: 2012-09-11
• [Presentation] Loss of IRF signaling contributes to the development of Helicobacter associated gastric carcinogenesis in vivo (2012)
  • Author(s): Shibata W, Yasuzaki H, Kubushiro Y, Hotta C, Tamura T, Maeda S
  • Organizer: Digestive Disease Week (DDW) 2012
  • Place of Presentation: サンディエゴ、アメリカ
  • Year and Date: 2012-05-20
• [Presentation] 骨髄系細胞分化での IRF8 と IRF4 の機能 (2012)
  • Author(s): 加藤隆幸,山本道雄,堀田千絵, 西山晃,高見正道,松山俊文,上條竜太郎,北川誠一,尾里啓子,田村智彦
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本文化会館(長野県)
  • Year and Date: 2012-03-31
• [Presentation] Interferon regulatory factor-5 in spinal microglia is a crucial transcription factor for the development of neuropathic pain (2012)
  • Author(s): Yoshinaga R, Tsuda M, Masuda T, Nishimoto N, Tozaki-Saitoh H, Tamura T, Inoue K
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2012-03-15
• [Presentation] IRF family transcription factor axis governs gene expression program in microglia that drives neuropathic pain (2012)
  • Author(s): Masuda T, Tsuda M, Yoshinaga R, Nishimoto N, Iwamoto S, Tamura T, Inoue K
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都国際会議場(京都府)
  • Year and Date: 2012-03-15
• [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)
  • Year and Date: 2011-12-14
• [Presentation] Transcription factor Egr-2 regulates IL-10 production induced by IL-27 in naive T cells (2011)
  • Author(s): Iwasaki Y, Yanai A, Okamura T, Sumitomo S, Shoda H, Tamura T, Fujio K, Yamamoto K
  • 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: 2011-11-29
• [Presentation] Regulation of the development of monocyte subsets by interferon regulatory factor 8 (2011)
  • 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)
  • Year and Date: 2011-11-28
• [Presentation] Interferon stimulation causes diverse changes in chromatin to regulate transcription (2011)
  • Author(s): Ozato K, Sarai N, Patel M, Debrosse M, Tamura T, Ura K
  • Organizer: 9th Joint Meeting of the International Society for Interferon and Cytokine Research (ISICR) and the International Cytokine Society (ICS)
  • Place of Presentation: フィレンツェ、イタリア
  • Year and Date: 2011-10-12
• [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: フィレンツェ、イタリア
  • Year and Date: 2011-10-11
• [Presentation] Interferon regulatory factor-8 は、神経損傷後に見られる脊髄ミクログリアの過活動状態への移行に重要な転写因子である (2011)
  • Author(s): 増田隆博,津田誠,吉永遼平,齊藤秀俊,田村智彦 ,井上和秀
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 山代温泉瑠璃光(石川県)
  • Year and Date: 2011-09-28
• [Presentation] 脊髄ミクログリアの interferon regulatory factor-5 は神経障害性疼痛の発現に重要な転写因子である (2011)
  • Author(s): 吉永遼平,津田誠,増田隆博,西本奈央,齋藤秀俊,田村智彦,井上和秀
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 山代温泉瑠璃光(石川県)
  • Year and Date: 2011-09-26
• [Presentation] IRF8 transcription factor directs microglia to be a hyperactive phenotype driving neuropathic pain (2011)
  • Author(s): Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Tamura T, Inoue K
  • Organizer: 10th Euroglia Meeting on Glial Cells in Health and Diseases
  • Place of Presentation: プラハ、チェコ
  • Year and Date: 2011-09-17
• [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
• [Presentation] 細菌感染時の生体防御反応におけるリンパ節CD169 陽性髄質マクロファージの役割の解明 (2011)
  • Author(s): 黒滝大翼,田村智彦,上出利光
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市ぶんかテンブス館(沖縄県)
  • Year and Date: 2011-07-01
• [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
• [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（ワークショップ）(招待講演)
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Loss of IRF signaling contributes to the development of Helicobacter associated gastric carcinogenesis in vivo
  • Author(s): Shibata W. et al.
  • Organizer: Digestive Disease Week 2012
  • Place of Presentation: San Diego Convention Center (アメリカ)
• [Presentation] Chromatin exchange in interferon induced transcription
  • Author(s): Ozato K. et al.
  • Organizer: 10th Joint Meeting of International Cytokine Society and International Society for Interferon and Cytokine Research
  • Place of Presentation: Centre International de Conferences Geneve (スイス)
• [Presentation] The transcription factor IRF8 in the pathogenesis and therapy of chronic myelogenous leukemia
  • Author(s): Tamura T.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
  • Invited
• [Presentation] ゲノム規模解析による転写因子IRF8を核とした単球分化制御プログラムの理解
  • Author(s): 田村智彦
  • Organizer: 文部科学省イノベーションシステム整備事業 先端融合領域イノベーション創出拠点形成プログラム「翻訳後修飾プロテオミクス医療研究拠点の形成」第4回公開シンポジウム
  • Place of Presentation: 横浜情報文化センター（神奈川県）
  • Invited
• [Presentation] Genome-wide analyses revealed the IRF8-KLF4 transcription factor cascade during monocyte differentiation
  • Author(s): Kurotaki D. 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）
• [Presentation] Impaired dendritic cell development in chronic myelogenous leukemia can be rescued by restoring expression of the transcription factor IRF8
  • Author(s): Watanabe 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）
• [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）
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~immunol/
• [Remarks] 横浜市立大学医学部 免疫学教室