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Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression

机译:早期生长反应基因1(Egr-1)调节HSV-1 ICP4和ICP22基因表达

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The molecular mechanisms mediating herpes simplex virus type 1 (HSV-1) gene silencing during latent infection are not clear. Five copies of early growth response gene 1 (Egr-1) binding elements were identified in the intron of HSV-1 ICP22 (infected cell protein No. 22) gene, leading to the hypothesis that Egr-1 binds to the viral genome and regulates the viral gene expression. Transient co-transfection assays indicated that Egr-1 negatively regulated the transcription of both full-length and intron-removed ICP22 promoters. The same assays also revealed that Egr-1 repressed ICP4 (infected cell protein No. 4) promoter activity in a dose-dependent manner but showed less inhibition when the intron was removed. Histone deacetylation was not involved in this regulation since histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-1-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Sp1 to the promoters and that the co-repressor Nab2 (NGFI-A/EGR1-binding protein) was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multifunctional transcription factor Egr-1 can repress HS V-1 immediate-early gene expression through the recruitment of co-repressor Nab2 and reduction of Sp 1 occupancy, and thus may play a critical role in HSV-1 gene silencing during latency.
机译:潜在感染过程中介导单纯疱疹病毒1型(HSV-1)基因沉默的分子机制尚不清楚。在HSV-1 ICP22(感染的细胞蛋白22号)基因的内含子中鉴定出五份早期生长反应基因1(Egr-1)结合元件,从而得出了Egr-1与病毒基因组结合并对其进行调节的假设。病毒基因表达。瞬时共转染测定表明,Egr-1负调控全长和内含子的ICP22启动子的转录。相同的测定还显示,Egr-1以剂量依赖的方式抑制ICP4(感染的4号细胞蛋白)启动子活性,但是当去除内含子时抑制作用较小。组蛋白脱乙酰基化不参与该调节,因为组蛋白脱乙酰基酶抑制剂曲古抑菌素A对Egr-1介导的抑制没有任何作用。染色质免疫沉淀分析表明,Egr-1减少了Sp1与启动子的结合,并且在Egr-1存在的情况下,共抑制因子Nab2(NGFI-A / EGR1结合蛋白)被募集到ICP4附近。这些结果表明,多功能转录因子Egr-1可通过募集协同阻遏物Nab2和减少Sp 1的表达来抑制HS V-1立即早期基因表达,因此可能在HSV-1基因沉默中起关键作用。在延迟期间。

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