PU.1 can regulate the ZNF300 promoter in APL-derived promyelocytes HL-60
PU.1 can regulate the ZNF300 promoter in APL-derived promyelocytes HL-60
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PU.1 可以调节 APL 来源的早幼粒细胞 HL-60 中的 ZNF300 启动子
DOI：
10.1016/j.leukres.2010.04.009
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发表时间：
2010-12-01
影响因子：
2.7
通讯作者：
Li, Wen-Xin
中科院分区：
文献类型：
--
作者：
Xu, Jun-Hua;Wang, Tao;Li, Wen-Xin
ZNF 300是一个典型的KRAB/C2 H2锌指基因，仅在高等哺乳动物中表达，在人类胚胎发育和某些疾病中起重要作用。我们的数据表明，ZNF 300的表达在不同的白血病原始细胞在新诊断的白血病患者的骨髓穿刺显着变化。为探讨ZNF 300基因的表达与白血病发生、发展和造血分化的关系，我们克隆了人ZNF 300基因启动子，并对其转录起始位点进行了鉴定。缺失和突变分析表明，骨髓特异性转录因子PU.1结合位点负责骨髓特异性调节ZNF 300启动子活性。此外，电泳迁移率变化和染色质免疫沉淀分析表明，PU. 1结合的PU. 1结合位点内ZNF 300启动子区域在体外和体内。PU.1过表达可提高ZNF 300启动子的活性，而PU.1表达沉默可显著降低ZNF 300启动子在髓源性HL-60细胞中的活性，但在T细胞Jurkat中无此作用。DMSO体外诱导HL-60细胞表达CD 11 b，表明ZNF 300的表达沿着PU. 1表达的上调。这些结果表明，ZNF 300被PU.1激活，并提示该调节可能参与白血病的发展和造血分化的进程。(C)2010爱思唯尔有限公司保留所有权利。
ZNF300, which plays the role in human embryonic development and some diseases, is a typical KRAB/C2H2 zinc finger gene expressed only in higher mammalians. Our data showed that expression of ZNF300 changed significantly in various leukemia blasts in the bone marrow aspirates of newly diagnosed leukemia patients. To investigate the potential relationship between expression of ZNF300 and the progression of leukemia development and hematopoietic differentiation, we cloned and characterized the putative human ZNF300 gene promoter and identified its transcription start sites (TSSs). Deletion and mutagenesis analysis demonstrated that a myeloid-specific transcription factor PU.1 binding site was responsible for myeloid-specific regulation of ZNF300 promoter activity. Furthermore, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that PU.1 bound to the PU.1 binding site within ZNF300 promoter region in vitro and in vivo. Overexpression of PU.1 elevated ZNF300 promoter activity, whereas silencing of PU.1 expression significantly reduced the activity in myeloid-derived HL-60 cell but not in T-cell Jurkat. In vitro induced HL-60 cells into CD11b expressing cells by DMSO demonstrated that ZNF300 was upregulated along with upregulation of PU.1 expression. These results demonstrated that ZNF300 was activated by PU.1 and suggested that the regulation may be involved in the progression of leukemia development and hematopoietic differentiation. (C) 2010 Elsevier Ltd. All rights reserved.