Induction of Myc-intron-binding polypeptides MIBP1 and RFX1 during retinoic acid-mediated differentiation of haemopoietic cells.
Induction of Myc-intron-binding polypeptides MIBP1 and RFX1 during retinoic acid-mediated differentiation of haemopoietic cells.
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DOI：
10.1042/bj3450535
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发表时间：
2000-02
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影响因子：
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通讯作者：
M. Zajac-Kaye;Noa Ben-Baruch;Evdokia Kastanos;Frederic J Kaye;Carmen J. Allegra
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文献类型：
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作者：
M. Zajac-Kaye;Noa Ben-Baruch;Evdokia Kastanos;Frederic J Kaye;Carmen J. Allegra
视黄酸介导的HL60细胞分化与染色质结构的改变（映射到c-myc基因内含子I内的蛋白质结合序列）和c-myc表达的下调有关。通过使用HeLa细胞提取物，我们先前鉴定了两种多肽，称为MIBP1 （myc内含子结合肽）和RFX1，它们在体内相互作用并结合内含子I元件；我们发现MIBP1/ rfx1结合位点的串联重复序列可以在异源启动子上表现出沉默活性。我们在未分化的HL60细胞中发现不存在p160 MIBP1和p130 RFX1。此外，我们发现视黄酸处理可以诱导MIBP1和RFX1蛋白，以及它们的dna结合活性，在HL60细胞的粒细胞分化中，具有与HeLa细胞相同的凝胶迁移模式。在缺乏p160 MIBP1和p130 RFX1的情况下，我们观察到在未分化的HL60细胞中检测到的凝胶迁移模式的改变反映了两种新的多肽p30和p97的结合，这两种多肽可以交联到相同的识别内含子序列。我们还发现，在视黄酸处理HL60细胞期间，MIBP1和RFX1诱导的时间过程与下调c-myc水平呈负相关。
Retinoic acid-mediated differentiation of HL60 cells is associated with an alteration of chromatin structure that maps to protein-binding sequences within intron I of the c-myc gene and with down-regulation of c-myc expression. By using HeLa cell extracts, we previously identified two polypeptides, designated MIBP1 (for Myc-intron-binding peptide) and RFX1, that interact in vivo and bind to the intron I element; we showed that tandem repeats of an MIBP1/RFX1-binding site can exhibit silencer activity on a heterologous promoter. Here we demonstrate that p160 MIBP1 and p130 RFX1 are absent from undifferentiated HL60 cells. In addition, we show that treatment with retinoic acid induces both MIBP1 and RFX1 protein, as well as their DNA-binding activity, upon granulocytic differentiation of HL60 cells, with a gel mobility pattern identical to that of HeLa cells. In the absence of p160 MIBP1 and p130 RFX1, we observed that the altered gel mobility-shift pattern detected in undifferentiated HL60 cells reflects the binding of two novel polypeptides, p30 and p97, that can be cross-linked to the same recognition intron sequence. We also show that the time course of MIBP1 and RFX1 induction is inversely correlated with the down-regulation of c-myc levels during the treatment of HL60 cells with retinoic acid.