GATA-1 directly regulates p21 gene expression during erythroid differentiation.
GATA-1 directly regulates p21 gene expression during erythroid differentiation.
复制标题
GATA-1在红系分化过程中直接调节P21基因表达。
DOI：
10.4161/cc.9.10.11602
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Skoultchi AI
中科院分区：
文献类型：
--
作者：
Papetti M;Wontakal SN;Stopka T;Skoultchi AI
谱系决定转录因子通过控制谱系特异性基因产物的合成以及细胞周期调节剂来协调细胞分化和增殖。加塔-1是红细胞生成的主要调节因子。它在调节红细胞特异性基因中的作用已被广泛研究，而它在控制调节细胞增殖的基因中的作用则知之甚少。加塔-1在红白血病细胞中的异位表达解除了对它们分化的阻断并导致终末细胞分裂。红白血病细胞重编程的早期事件是诱导细胞周期蛋白依赖性激酶抑制剂p21。值得注意的是，p21的异位表达也诱导红白血病细胞分化。我们现在报道加塔-1直接调节红白血病细胞和正常红系祖细胞中p21基因的转录。使用报告，电泳迁移率变动，染色质免疫沉淀试验，我们表明，加塔-1刺激p21基因转录的结合，在上游区域的p21基因启动子的共识结合位点。该活性还取决于转录起始位点附近Sp1/KLF样因子的结合位点。我们的研究结果表明，p21是一个关键的下游基因靶和效应的加塔-1在红细胞终末分化。
Lineage-determination transcription factors coordinate cell differentiation and proliferation by controling the synthesis of lineage-specific gene products as well as cell cycle regulators. GATA-1 is a master regulator of erythropoiesis. Its role in regulating erythroid-specific genes has been extensively studied, whereas its role in controlling genes that regulate cell proliferation is less understood. Ectopic expression of GATA-1 in erythroleukemia cells releases the block to their differentiation and leads to terminal cell division. An early event in reprogramming the erythroleukemia cells is induction of the cyclin-dependent kinase inhibitor p21. Remarkably, ectopic expression of p21 also induces the erythroleukemia cells to differentiate. We now report that GATA-1 directly regulates transcription of the p21 gene in both erythroleukemia cells and normal erythroid progenitors. Using reporter, electrophoretic mobility shift, and chromatin immunoprecipitation assays, we show that GATA-1 stimulates p21 gene transcription by binding to consensus binding sites in the upstream region of the p21 gene promoter. This activity is also dependent on a binding site for Sp1/KLF-like factors near the transcription start site. Our findings indicate that p21 is a crucial downstream gene target and effector of GATA-1 during red blood cell terminal differentiation.
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