Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics
Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics
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DOI：
10.1038/nsmb713
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发表时间：
2004-01-01
影响因子：
16.8
通讯作者：
Groudine, M
中科院分区：
文献类型：
--
作者：
Brand, M;Ranish, JA;Groudine, M
在红系分化过程中，β-珠蛋白基因表达受基因座控制区（LCR）调控。转录因子NF-E2 p18/MafK在该区域内结合，并且对于鼠红白血病（MEL）细胞中的β-珠蛋白表达是必需的。在这里，我们使用同位素编码的亲和标签（ICAT）技术的定量质谱比较蛋白质与NF-E2 p18/MafK在分化过程中相互作用。我们的研究结果将MafK定义为在红系分化过程中从抑制模式转变为激活模式的“双功能”分子。MafK二聚化配偶体从Bach 1到NF-E2 p45的交换是从抑制状态转换到活性状态的关键步骤。这种转变与MafK与辅抑制因子和辅激活因子相互作用的变化有关。因此，我们的研究结果表明，除了作为一个顺式作用激活剂的β-珠蛋白基因表达分化的红系细胞中的作用，LCR也促进了积极的镇压β-珠蛋白转录终末分化前的承诺细胞。
During erythroid differentiation, beta-globin gene expression is regulated by the locus control region (LCR). The transcription factor NF-E2p18/MafK binds within this region and is essential for beta-globin expression in murine erythroleukemia (MEL) cells. Here we use the isotope-coded affinity tag (ICAT) technique of quantitative mass spectrometry to compare proteins interacting with NF-E2p18/MafK during differentiation. Our results define MafK as a 'dual-function' molecule that shifts from a repressive to an activating mode during erythroid differentiation. The exchange of MafK dimerization partner from Bach1 to NF-E2p45 is a key step in the switch from the repressed to the active state. This shift is associated with changes in the interaction of MafK with co-repressors and co-activators. Thus, our results suggest that in addition to its role as a cis-acting activator of beta-globin gene expression in differentiated erythroid cells, the LCR also promotes an active repression of beta-globin transcription in committed cells before terminal differentiation.