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
复制标题
DOI：
10.1042/0264-6021:3450535
复制
发表时间：
2000-02-01
影响因子：
4.1
通讯作者：
Allegra, C
中科院分区：
文献类型：
--
作者：
Zajac-Kaye, M;Ben-Baruch, N;Allegra, C
视黄酸介导的HL 60细胞分化与染色质结构的改变有关，该结构映射到c-myc基因内含子I内的蛋白结合序列，并与c-myc表达下调有关。通过使用HeLa细胞提取物，我们以前确定了两种多肽，指定MIBP 1（Myc内含子结合肽）和RFX 1，在体内相互作用，并结合到内含子I元件，我们表明，串联重复的MIBP 1/RFX 1结合位点可以表现出沉默活性的异源启动子。在这里，我们证明，p160 MIBP 1和p130 RFX 1是缺乏未分化的HL 60细胞。此外，我们表明，视黄酸治疗诱导MIBP 1和RFX 1蛋白，以及它们的DNA结合活性，粒细胞分化的HL 60细胞，与凝胶迁移率模式相同的HeLa细胞。在没有p160 MIBP 1和p130 RFX 1的情况下，我们观察到在未分化的HL 60细胞中检测到的改变的凝胶迁移率变化模式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。我们还表明，MIBP 1和RFX 1诱导的时间过程中，与下调的c-myc水平的HL 60细胞与视黄酸的治疗过程中呈负相关。
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.