In vivo identification of novel STAT5 target genes.

In vivo identification of novel STAT5 target genes.
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新型STAT5靶基因的体内鉴定。

DOI:
10.1093/nar/gkn271
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发表时间:
2008-06
影响因子:
14.9
通讯作者:
Rascle, Anne
Rascle, Anne
中科院分区:
生物学2区
文献类型:
--
作者:
Basham, Beth;Sathe, Manjiri;Grein, Jeffrey;McClanahan, Terrill;D'Andrea, Annalisa;Lees, Emma;Rascle, Anne

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STAT 5A和STAT 5 B蛋白属于信号转导子和转录激活子家族。它们由两个独立的基因编码,其氨基酸序列具有91%的同一性。尽管它们高度保守,但STAT 5A和STAT 5 B发挥非冗余功能,至少部分地由靶基因活化的差异引起。为了更好地表征STAT 5A和STAT 5 B在基因调控中的差异贡献,我们使用小干扰RNA对STAT 5A和STAT 5 B进行单或双敲低。随后对IL-3刺激的Ba/F3-β细胞进行基因表达谱分析和RT-qPCR分析,鉴定了推定的新型STAT 5靶基因。染色质免疫沉淀试验分析相应的基因位点确定不寻常的STAT 5结合位点相比,传统的STAT 5响应元件。一些STAT 5靶点在几种人类癌症中上调,表明它们可能代表STAT 5相关恶性肿瘤中的潜在致癌基因。
STAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by two separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knockdown of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-β cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.
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发表时间: 2004
影响因子: 4.9
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