Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes
Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes
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DOI：
10.1016/s0301-472x(01)00655-5
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发表时间：
2001-07-01
影响因子：
2.6
通讯作者：
Nakamura, T
中科院分区：
文献类型：
--
作者：
Fujino, T;Yamazaki, Y;Nakamura, T
客观的。同源盒基因 Hoxb8 在小鼠骨髓单核细胞系 WEHI-3B 中由于脑池内 A 颗粒整合而被激活。 Hoxa9 和 Meis1 之间的协同激活是由 BXH2 小鼠髓系白血病和髓系白血病细胞系 M1 中的逆转录病毒整合诱导的。本研究旨在检查 WENI-3R 中可能的 Meis 基因激活和同源框蛋白的协同 DNA 结合，并揭示 Hox 和 Meis 基因在髓系分化中的具体作用。 材料和方法。进行Northern印迹分析和逆转录酶聚合酶链反应来检查同源框基因表达。进行电泳迁移率变动测定来评估同源框蛋白的 DNA 结合。粒细胞集落刺激因子诱导32Dc13的骨髓分化，结果。 Meis2 与 Herbs 在 WEHI-3B 细胞中共同激活。在 WEHI-3B 和 32Dc13 中观察到包括 Hox、Meis 和 Pbx 在内的 DNA-蛋白质复合物，Hoxa9、Hoxb8、Meis1 和 Meis2 的表达和 DNA 结合复合物在 32Dc13 细胞的骨髓分化过程中下调。 Hox或Meis基因的强制表达抑制了32Dc13的髓系分化，结论，结果表明Meis2是髓系白血病发生的重要Meis基因，并且Hox和Meis是通过分化阻断导致髓系白血病发生的重要基因，(C)2001国际实验血液学会。由爱思唯尔科学公司出版
Objective. The homeobox gene Hoxb8 is activated in the murine myelomonocytic cell line WEHI-3B as a result of intracisternal A particle integration. Cooperative activation between Hoxa9 and Meis1 is induced by retroviral integration in BXH2 murine myeloid leukemias and the myeloid leukemia cell line M1, The present study was conducted to examine possible Meis gene activation and cooperative DNA binding of homeobox proteins in WENI-3R and to reveal the specific role of Hox and Meis genes in myeloid differentiation.Materials and Methods. Northern blot analysis and reverse transcriptase polymerase chain reaction were performed to examine homeobox genes expression. Electrophoretic mobility shift assay was performed to evaluate DNA binding of homeobox proteins. Myeloid differentiation of 32Dc13 was induced by granulocyte colony-stimulating factor,Results. Meis2 was coactivated with Herbs in WEHI-3B cells. DNA-protein complexes including Hox, Meis, and Pbx were observed in WEHI-3B and 32Dc13, Expression and the DNA-binding complex of Hoxa9, Hoxb8, Meis1, and Meis2 were down-regulated during myeloid differentiation of 32Dc13 cells. Enforced expression of Hox or Meis genes inhibited myeloid differentiation of 32Dc13,Conclusion, The results indicate that Meis2 is an important Meis gene for myeloid leukemogenesis and that Hox and Meis are important genes for myeloid leukemogenesis through differentiation block, (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.