Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip.
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip.
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DOI：
10.1186/gb-2008-9-11-r166
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发表时间：
2008
期刊：
影响因子：
12.3
通讯作者：
Mercola, Dan
中科院分区：
文献类型：
--
作者：
Arora, Shilpi;Wang, Yipeng;Jia, Zhenyu;Vardar-Sengul, Saynur;Munawar, Ayla;Doctor, Kutbuddin S.;Birrer, Michael;McClelland, Michael;Adamson, Eileen;Mercola, Dan
紫外线对前列腺细胞的刺激引起依赖于锌指转录因子Egr1的凋亡反应；在这种反应中Egr1的下游靶标被确定。紫外线照射激活了表皮生长因子受体，诱导了Egr1的表达，促进了多种细胞类型的凋亡。我们在人类致癌的前列腺癌M12细胞中使用芯片协议检验了Egr1调节介导这一过程的基因的假说。紫外光照射导致288个基因启动子与Egr1显著结合。一个主要的功能亚群由凋亡相关基因组成。最大的24个基因亚组属于表皮生长因子受体-信号转导通路。Egr1启动子结合对靶基因的基因表达有显著影响。用常规染色质免疫沉淀和实时定量聚合酶链式反应验证启动子结合和表达的变化。小干扰RNA实验证实了Egr1在基因调控中的特殊作用。紫外线刺激促进了M12细胞的生长停滞和凋亡，我们的数据清楚地表明，表皮生长因子受体的下游靶点，即EGR1，介导了这一凋亡反应。我们的研究还发现了许多以前未知的Egr1靶点。这些基因包括FasL、Max和RRAS2，它们可能在细胞凋亡反应/生长停滞中发挥作用。我们的结果表明，M12细胞在紫外线刺激下经历Egr1依赖的凋亡反应，并导致Egr1下游靶点的确定，Egr1介导表皮生长因子受体的功能。
UV stimulation of prostate cells causes an apoptotic response that is dependent on the zinc finger transcription factor Egr1; downstream targets of Egr1 in this response were identified. UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional chromatin immunoprecipitation and quantitative real time PCR were used to validate promoter binding and expression changes. Small interfering RNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that a downstream target of the epidermal growth factor receptor, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest. Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV stimulation and led to the identification of downstream targets of Egr1, which mediate epidermal growth factor receptor function.
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DOI：
10.1083/jcb.133.1.211
发表时间：
1996-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Huang RP;Wu JX;Fan Y;Adamson ED
通讯作者：
Adamson ED
影响因子：
12.4
作者：
Bellot, G.;Cartron, P. -F.;Vallette, F. M.
通讯作者：
Vallette, F. M.
影响因子：
20.3
作者：
Hoemme, Claudia;Peerzada, Abdul;Mueller-Tidow, Carsten
通讯作者：
Mueller-Tidow, Carsten
影响因子：
64.5
作者：
CALL, KM;GLASER, T;HOUSMAN, DE
通讯作者：
HOUSMAN, DE
影响因子：
56.9
作者：
LANGECARTER, CA;JOHNSON, GL
通讯作者：
JOHNSON, GL