Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates DIk1 expression
Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates DIk1 expression
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DOI：
10.1002/jcb.10190
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Briggs, RC
中科院分区：
文献类型：
--
作者：
Doggett, YL;Briggs, JA;Briggs, RC
人髓样核分化抗原（MNDA）是一种造血细胞特异性核蛋白。MNDA和其他相关基因产物与参与调节特定基因转录的大量蛋白质相互作用并改变其活性。MNDA和相关基因表现出表达特征，这表明除了介导干扰素的作用之外，特定细胞谱系具有独特的功能。人K562髓系细胞不表达MNDA，与表达MNDA的细胞系（HL-60、U937和THP 1）相比相对不成熟。通过使用稳定的逆转录病毒介导的基因转移产生表达MNDA的K562细胞，然后评估转录谱，来测试MNDA影响特定基因表达的假设。两个含有Ka共2，350个已知基因cDNA的微阵列显示在表达MNDA的K562细胞克隆中Dlk 1表达的特异性上调。真实的时间定量RT-PCR分析证实了在表达MNDA的K562细胞的两个克隆中Dlk 1的平均超过3倍和7倍的上调。北方印迹法也证实了对Dlk 1的影响，Dlk 1是正常造血所必需的，并且异常表达是骨髓增生异常综合征的建议标志物。诱导红系和巨核细胞分化后转录谱的额外筛选显示，MNDA的存在没有改变额外的基因转录本。这些结果表明，MNDA改变了正常造血所必需的基因的表达。(C)2002 Wiley-Liss，Inc.
The human myeloid nuclear differentiation antigen (MNDA) is a hematopoietic cell specific nuclear protein. MNDA and other related gene products interact with and alter the activity of a large number of proteins involved in regulating specific gene transcription. MNDA and related genes exhibit expression characteristics, which suggest functions unique to specific lineages of cells, in addition to mediating the effects of interferons. Cells of the human K562 myeloid line do not express MNDA and are relatively immature compared to lines that express MNDA (HL-60, U937, and THP1). The hypothesis that MNDA influences the expression of specific genes was tested by creating MNDA expressing K562 cells using stable retroviral mediated gene transfer followed by evaluation of transcription profiles. Two microarrays containing Ka total of 2,350 cDNAs of known genes showed a specific up-regulation of Dlk1 expression in MNDA expressing K562 cell clones. Real time quantitative RT-PCR analysis confirmed an average of over 3- and 7-fold upregulation of Dlk1 in two clones of MNDA expressing K562 cells. The effects on Dlk1 were also confirmed by Northern blotting, Dlk1 is essential for normal hematopoiesis and abnormal expression is a proposed marker of myelodysplastic syndrome. Additional screening of transcription profiles after induced erythroid and megakaryoblastic differentiation showed no additional gene transcripts altered by the presence of MNDA. These results indicate that MNDA alters expression of a gene essential for normal hematopoiesis. (C) 2002 Wiley-Liss, Inc.