The hematopoietic regulator, ELF-1, enhances the transcriptional response to Interferon-β of the OAS1 anti-viral gene.
The hematopoietic regulator, ELF-1, enhances the transcriptional response to Interferon-β of the OAS1 anti-viral gene.
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DOI：
10.1038/srep17497
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发表时间：
2015-12-08
影响因子：
4.6
通讯作者：
Uchiumi F
中科院分区：
文献类型：
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作者：
Larsen S;Kawamoto S;Tanuma S;Uchiumi F
干扰素治疗在治疗癌症、血液病和病毒引起的疾病方面是有效的。经典的JAK/STAT途径是干扰素信号转导导致转录活性改变的重要途径，但仅凭这一途径并不能解释细胞对干扰素的全部反应。基因启动子包含顺式作用序列，允许精确和上下文结合控制基因表达的转录因子。以干扰素的转录反应为起点，我们报道在干扰素刺激基因的近端启动子中有高频率的串联GGAA基序，这表明了一个关键的调控作用。以具有良好特性的抗病毒基因OAS1为例，我们通过突变分析证明了该启动子在干扰素应答中的调节作用。此外，我们还发现ELF-1是该基序的直接结合因子。此外，在干扰素刺激后，RB1和SP1因子被重新招募到启动子。ELF-1过表达增强，而阻断ELF-1则抑制干扰素刺激的OAS1的完全激活。总的来说，ELF-1在OAS1启动子上结合了一个重要的复制的GGAA顺式作用元件，并与RB1和SP1的招募合作，有助于调节对干扰素刺激的反应。
Interferon (IFN) therapy is effective in treating cancers, haematological and virus induced diseases. The classical Jak/Stat pathway of IFN signal transduction leading to changes in transcriptional activity is well established but alone does not explain the whole spectrum of cellular responses to IFN. Gene promoters contain cis-acting sequences that allow precise and contextual binding of transcription factors, which control gene expression. Using the transcriptional response to IFN as a starting point we report a high frequency of tandem GGAA motifs in the proximal promoters of Interferon stimulated genes, suggesting a key regulatory action. Utilizing the well-characterized anti-viral gene, OAS1, as an example Interferon stimulated gene promoter containing such a duplicated GGAA motif, we have demonstrated a regulatory role of this promoter in response to IFN by mutation analysis. Furthermore, we identified ELF-1 as a direct binding factor at this motif. Additionally, recruitment of RB1 and SP1 factors to the promoter following IFN stimulation is shown. ELF-1 overexpression enhanced and knockdown of ELF-1 inhibited full activation of OAS1 by IFN stimulation. Collectively, ELF-1 binds an important duplicated GGAA cis-acting element at the OAS1 promoter and in cooperation with RB1 and SP1 recruitment contributes to regulation in response to IFN stimulation.
影响因子：
15.3
作者：
John, S;Marais, R;Child, R;Light, Y;Leonard, WJ
通讯作者：
Leonard, WJ