Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells
Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells
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DOI：
10.1128/mcb.12.9.4104-4111.1992
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发表时间：
1992-09
影响因子：
5.3
通讯作者：
L. Sistonen;K. Sarge;B. Phillips;K. Abravaya;R. Morimoto
中科院分区：
文献类型：
--
作者：
L. Sistonen;K. Sarge;B. Phillips;K. Abravaya;R. Morimoto
氯化血红素诱导人K562红白血病细胞的非终末分化，这伴随着某些红系细胞特异性基因的表达，如胚胎和胎儿球蛋白，以及应激基因hsp 70，hsp 90和grp 78/BiP的表达升高。以前的研究表明，在热休克期间，hsp 70在氯化血红素处理的细胞中的转录诱导是由热休克转录因子（HSF）的激活介导的，热休克转录因子（HSF）与热休克元件（HSE）结合。我们在这里报告，氯化血红素激活DNA结合活性的HSF 2，而热休克诱导主要是DNA结合活性的一个独特的因素，HSF 1。这构成了体内HSF 2活化的第一个实例。氯化血红素和热休克处理导致在体外凝胶迁移率变动分析的HSF-HSE复合物的等效水平，但热休克诱导的HSF比氯化血红素诱导的HSF刺激hsp 70基因的转录少得多。基因组足迹实验表明，氯化血红素诱导的HSF和热休克诱导的HSF，HSF 2和HSF 1，分别占据HSE的人热休克蛋白70启动子以类似但不相同的方式。我们推测HSF 1和HSF 2的占用率和/或转录能力的差异解释了所观察到的刺激hsp 70基因转录的差异。
Hemin induces nonterminal differentiation of human K562 erythroleukemia cells, which is accompanied by the expression of certain erythroid cell-specific genes, such as the embryonic and fetal globins, and elevated expression of the stress genes hsp70, hsp90, and grp78/BiP. Previous studies revealed that, as during heat shock, transcriptional induction of hsp70 in hemin-treated cells is mediated by activation of heat shock transcription factor (HSF), which binds to the heat shock element (HSE). We report here that hemin activates the DNA-binding activity of HSF2, whereas heat shock induces predominantly the DNA-binding activity of a distinct factor, HSF1. This constitutes the first example of HSF2 activation in vivo. Both hemin and heat shock treatments resulted in equivalent levels of HSF-HSE complexes as analyzed in vitro by gel mobility shift assay, yet transcription of the hsp70 gene was stimulated much less by hemin-induced HSF than by heat shock-induced HSF. Genomic footprinting experiments revealed that hemin-induced HSF and heat shock-induced HSF, HSF2, and HSF1, respectively, occupy the HSE of the human hsp70 promoter in a similar yet not identical manner. We speculate that the difference in occupancy and/or in the transcriptional abilities of HSF1 and HSF2 accounts for the observed differences in the stimulation of hsp70 gene transcription.