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首页> 外文期刊>Molecular and Cellular Biology >YY1 represses rat serum amyloid A1 gene transcription and is antagonized by NF-kappa B during acute-phase response.
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YY1 represses rat serum amyloid A1 gene transcription and is antagonized by NF-kappa B during acute-phase response.

机译：YY1抑制大鼠血清淀粉样蛋白A1基因转录，并​​在急性期反应中被NF-κB拮抗。

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Serum amyloid A (SAA), one of the major acute-phase proteins, increases several hundredfold in concentration in plasma following acute inflammation, primarily as a result of a 200-fold increase in its transcriptional rate. Functional analysis of the rat SAA1 promoter has identified a 65-bp cytokine response unit (CRU; positions -135 to -71) that could confer cytokine responsiveness on a heterologous promoter. Within this CRU, two cis-regulatory elements, corresponding to NF-kappa B- and C/EBP-binding sites, were found to be functionally important and exerted synergistic effects on induced SAA1 expression. In this report, we show that a third transcription factor interacts with the CRU through a region located between the NF-kappa B- and C/EBP-binding sites. On the basis of its gel mobility shift patterns, ubiquitous binding activity, sequence specificity of DNA binding, zinc-dependent binding activity, and gel mobility supershift by specific antibodies, we concluded that this factor is identical to YY1. Methylation interference studies revealed that YY1 binding sequences overlapped with those of NF-kappa B, and gel mobility studies showed that NF-kappa binding to the CRU was effectively inhibited by YY1. Consistent with its presumed antagonistic role to NF-kappa B, YY1 exerted a negative effect on SAA1 expression, whereas disruption of its binding in the promoter elevated basal and cytokine-induced activities. Furthermore, overexpression of YY1 trans-repressed SAA1 promoter activity. Thus, our results demonstrate that SAA1 expression is tightly regulated by an on-off switch of activators and repressors, presumably to ensure that it is expressed only under appropriate physiological conditions.
机译：血清淀粉样蛋白A（SAA）是一种主要的急性期蛋白，在急性炎症后血浆中的浓度会增加几百倍，这主要是由于其转录速率增加了200倍。大鼠SAA1启动子的功能分析已鉴定出65 bp的细胞因子应答单元（CRU; -135至-71位），可赋予异源启动子细胞因子应答性。在该CRU中，发现两个顺式调节元件，分别对应于NF-κB和C / EBP结合位点，在功能上很重要，并且对诱导的SAA1表达起协同作用。在此报告中，我们显示了第三转录因子通过位于NF-κB-和C / EBP结合位点之间的区域与CRU相互作用。根据其凝胶迁移率变化模式，普遍存在的结合活性，DNA结合的序列特异性，锌依赖性结合活性和特异性抗体引起的凝胶迁移率超迁移，我们得出结论，该因子与YY1相同。甲基化干扰研究表明，YY1结合序列与NF-κB的序列重叠，而凝胶迁移率研究表明，NF-κ与CRU的结合受到YY1的有效抑制。 YY1与其假定的对NF-κB的拮抗作用相一致，对SAA1表达产生负面影响，而破坏其在启动子中的结合则增加了基础和细胞因子诱导的活性。此外，YY1的过表达抑制SAA1启动子活性。因此，我们的结果表明，SAA1表达受到激活剂和阻遏物的通断开关的严格调节，以确保仅在适当的生理条件下表达。

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