Knockdown of ZNF268, which is transcriptionally downregulated by GATA-1, promotes proliferation of K562 cells.
Knockdown of ZNF268, which is transcriptionally downregulated by GATA-1, promotes proliferation of K562 cells.
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DOI：
10.1371/journal.pone.0029518
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Zeng Y;Wang W;Ma J;Wang X;Guo M;Li W
人ZNF 268基因编码一种典型的KRAB-C2 H2锌指蛋白，可能参与造血和白血病的发生。最近的一项微阵列研究表明，ZNF 268的表达在红细胞生成过程中持续下降。然而，ZNF 268在造血过程中的分子调控机制还不清楚。在这里，我们发现红细胞生成的主要调节因子加塔-1抑制了ZNF 268的启动子活性和转录。电泳迁移率改变分析和染色质免疫沉淀分析表明，加塔-1直接结合在ZNF 268启动子的加塔结合位点在体外和体内。用特异性siRNA敲低K562红白血病细胞中的ZNF 268可加速细胞增殖，抑制细胞凋亡，并减少红系特异性发育标记物的表达。它还促进裸鼠皮下K562衍生肿瘤的生长。这些结果表明，ZNF 268是加塔-1的关键下游靶标和效应子。提示加塔-1下调ZNF 268的表达在促进K562红白血病细胞生长和抑制其分化中具有重要作用。
The human ZNF268 gene encodes a typical KRAB-C2H2 zinc finger protein that may participate in hematopoiesis and leukemogenesis. A recent microarray study revealed that ZNF268 expression continuously decreases during erythropoiesis. However, the molecular mechanisms underlying regulation of ZNF268 during hematopoiesis are not well understood. Here we found that GATA-1, a master regulator of erythropoiesis, repressed the promoter activity and transcription of ZNF268. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that GATA-1 directly bound to a GATA binding site in the ZNF268 promoter in vitro and in vivo. Knockdown of ZNF268 in K562 erythroleukemia cells with specific siRNA accelerated cellular proliferation, suppressed apoptosis, and reduced expression of erythroid-specific developmental markers. It also promoted growth of subcutaneous K562-derived tumors in nude mice. These results suggest that ZNF268 is a crucial downstream target and effector of GATA-1. They also suggest the downregulation of ZNF268 by GATA-1 is important in promoting the growth and suppressing the differentiation of K562 erythroleukemia cells.
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影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
影响因子：
30.8
作者：
SIMON, MC;PEVNY, L;ORKIN, SH
通讯作者：
ORKIN, SH
影响因子：
8
作者：
Hoffman, B;Amanullah, A;Liebermann, DA
通讯作者：
Liebermann, DA
DOI：
10.1016/s0167-4781(01)00194-4
发表时间：
2001-04-16
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Gou, DM;Sun, Y;Li, WX
通讯作者：
Li, WX
人锌指 ZNF268 基因的转录需要基因内启动子元件
影响因子：
4.8
作者：
Guo, Ming-Xiong;Wang, Di;Li, Wen-Xin
通讯作者：
Li, Wen-Xin