Erythroid-induced commitment of K562 cells results in clusters of differentially expressed genes enriched for specific transcription regulatory elements
Erythroid-induced commitment of K562 cells results in clusters of differentially expressed genes enriched for specific transcription regulatory elements
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DOI：
10.1152/physiolgenomics.00028.2004
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发表时间：
2004-09-16
影响因子：
4.6
通讯作者：
Surrey, S
中科院分区：
文献类型：
--
作者：
Addya, S;Keller, MA;Surrey, S
了解胎儿和胚胎血红蛋白表达的调节是至关重要的，因为它们的表达降低了镰状细胞病和β地中海贫血的临床严重程度。K562细胞是一种人红白血病细胞系，可沿沿着红系或巨核系分化，并可作为调节胎儿/胚胎珠蛋白表达的模型。我们使用微阵列表达谱来表征K562细胞用氯化血红素（一种红系定型诱导剂）处理不同时间的转录组。约5,000个基因的表达与治疗无关。比较表达分析（CEA）确定了899个差异表达的基因;自组织映射（SOM）算法分析将425个基因聚类为8种不同的表达模式，其中322个是两种分析共有的。通过实时RT-PCR验证一个基因子集的差异表达。通过PAINT v3.0软件对差异表达基因的5 '侧翼区的分析显示特异性转录调控元件（TREs）的富集，一些定位于不同的表达簇。这一发现表明簇成员通过特定的TREs进行协调调节。最后，我们的研究结果提供了新的见解限速步骤在这些细胞中含血红素的血红蛋白四聚体的外观。
Understanding regulation of fetal and embryonic hemoglobin expression is critical, since their expression decreases clinical severity in sickle cell disease and beta-thalassemia. K562 cells, a human erythroleukemia cell line, can differentiate along erythroid or megakaryocytic lineages and serve as a model for regulation of fetal/embryonic globin expression. We used microarray expression profiling to characterize transcriptomes from K562 cells treated for various times with hemin, an inducer of erythroid commitment. Approximately 5,000 genes were expressed irrespective of treatment. Comparative expression analysis (CEA) identified 899 genes as differentially expressed; analysis by the self-organizing map (SOM) algorithm clustered 425 genes into 8 distinct expression patterns, 322 of which were shared by both analyses. Differential expression of a subset of genes was validated by real-time RT-PCR. Analysis of 5'-flanking regions from differentially expressed genes by PAINT v3.0 software showed enrichment in specific transcription regulatory elements (TREs), some localizing to different expression clusters. This finding suggests coordinate regulation of cluster members by specific TREs. Finally, our findings provide new insights into rate-limiting steps in the appearance of heme-containing hemoglobin tetramers in these cells.