Analysis of Genome Operating Systems for Immune Network by Polycomb Group Genes.

通过 Polycomb 组基因分析免疫网络的基因组操作系统。

• 批准号: 12490025
• 负责人: KANNO Masamoto
• 金额: $ 9.09万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12490025/
• 关键词: Thymus; T-lymphocyte; immature diffarentitation; Folycomb group gene; Protein complex; Chromatin; リンパ球初期分化; 転写制御; ポリコーム; 細胞周期; 細胞死; 遺伝子欠損マウス; 免疫不全; 維持機構

The Polycomb group (PcG) genes products form protein complexes in mammalian cell nuclei that contribute to maintain chromatin silencing of target genes. Among mammalian PcG homologues, mel-18 has been elucidated to regulate cell cycle progression, cell death, or senescence through analyses of knockout/Tg mice. Its product participatesin Polycomb protein complexes, whose existences in cell nuclei are displayed speckled distributions, overlapped with heterochromatin areas in immunohistochemical examinations.We describe that the defect in thymic T-lymphocyte development of mel-18 deficient mice implies the involvement of mel-18 in the maintenance of immature lymphocyte by regulating their survival via controlling the expression of some commitment and survival factors including subgroup of bcl-2 family. Therefore we would like to propose our results as the regulation mechanisms to control the balance between proliferation and cell death in lymphocyte development, especially ETP cell of DN1 fraction and small cell (E cell) of DN3 fraction just before the beta-selection of immature thymocyte by destabilization of chromatin silencing Polycomb protein complex.

Polycomb 组 (PcG) 基因产物在哺乳动物细胞核中形成蛋白质复合物，有助于维持靶基因的染色质沉默。在哺乳动物 PcG 同系物中，通过对基因敲除/Tg 小鼠的分析，已阐明 mel-18 可以调节细胞周期进程、细胞死亡或衰老。其产物参与Polycomb蛋白复合物，其在细胞核中呈斑点状分布，在免疫组化检查中与异染色质区域重叠。我们描述mel-18缺陷小鼠胸腺T淋巴细胞发育缺陷提示mel-18通过控制某些淋巴细胞的表达来调节淋巴细胞的存活，从而参与维持未成熟淋巴细胞的生存。 承诺和生存因素，包括 bcl-2 家族亚组。因此，我们希望提出我们的结果作为控制淋巴细胞发育中增殖和细胞死亡之间平衡的调节机制，特别是在通过染色质沉默Polycomb蛋白复合物的不稳定对未成熟胸腺细胞进行β选择之前的DN1级分的ETP细胞和DN3级分的小细胞（E细胞）。

项目成果

Sakai R, Kajiume T, Inoue H, Kanno R, Miyazaki M, Ninomiya Y, and Kanno M.: "TCDD treatment eliminates the long-term reconstitution activity of hematopoietic stem cells."Toxicol. Sci.. 72. 84-91 (2003)

Sakai R、Kajiume T、Inoue H、Kanno R、Miyazaki M、Ninomiya Y 和 Kanno M.：“TCDD 治疗消除了造血干细胞的长期重建活性。”Toxicol。

Fujisaki S, Ninomiya Y, Ishihara H, Miyazaki M, Kanno R, Asahara T, and Kanno M.: "Dimerization of the Polycomb-group protein Mel-18 is regulated by PKC phosphoryjation."BBRC. 300. 135-140 (2003)

Fujisaki S、Ninomiya Y、Ishihara H、Miyazaki M、Kanno R、Asahara T 和 Kanno M.：“多梳蛋白 Mel-18 的二聚化受 PKC 磷酸化的调节。”BBRC。

Yamasaki, M., Sasho, S., Moriya, H., Kanno, M., Harada, M., Kamada, N., Shimizu, E., Nakayama, T., Taniguchi, M: "Extrathymic development of Vall T cells in placenta during pregnancy and their possible physiological role"J.Immunology. 166. 7244-7249 (2001

Yamasaki, M.、Sasho, S.、Moriya, H.、Kanno, M.、Harada, M.、Kamada, N.、Shimizu, E.、Nakayama, T.、Taniguchi, M：“Vall T 的胸腺外发育

Fujisaki S: "Dimerization of the Polycomb-group protein Mel-18 is regulated by PKC phosphorylation"BBRC. 300. 135-140 (2003)

Fujisaki S：“多梳蛋白 Mel-18 的二聚化受 PKC 磷酸化的调节”BBRC。

Miyazaki, K., Inoue, H., Onai, N., Ishihara, H., Kanno, M.: "Chemokine-mediated thymopoiesis is regulated by a mammalian Polycomb group gene, mel-18"Immunol Lett.. 80. 139-143 (2002)

Miyazaki, K.、Inoue, H.、Onai, N.、Ishihara, H.、Kanno, M.：“趋化因子介导的胸腺生成受哺乳动物 Polycomb 组基因 mel-18 调节”Immunol Lett.. 80. 139