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首页> 外文期刊>Cytokine >Human interleukin-5 expression is synergistically regulated by histone acetyltransferase CBP/p300 and transcription factors C/EBP, NF-AT and AP-1.
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Human interleukin-5 expression is synergistically regulated by histone acetyltransferase CBP/p300 and transcription factors C/EBP, NF-AT and AP-1.

机译：人白介素5的表达受组蛋白乙酰转移酶CBP / p300和转录因子C / EBP，NF-AT和AP-1协同调节。

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摘要

Interleukin-5 (IL-5) plays a central role in the growth and differentiation of eosinophils and contributes to several disease states including asthma. There has been considerable interest in the identification of the transcriptional mechanisms controlling the synthesis of this cytokine. The regulation of IL-5 message is primarily at the level of transcription and is likely to be controlled, to a large extent, by regulatory elements in the promoter region that can influence the transcriptional activity of the gene. In this study, we performed a series of transient transfection experiments with IL-5 promoter-reporter gene construct and expression plasmid for E1A, an inhibitor of CBP/p300, or for the CBP/p300-binding defective E1ADelta2-36. The results showed that E1A repressed IL-5 promoter activity, while E1ADelta2-36 had no effect on it. This suggested that CBP/p300 was involved in regulation of IL-5 gene expression. Transcriptional coactivator CBP/p300 and transcription factors C/EBP, NF-AT, and c-Fossynergistically activated IL-5 promoter. Furthermore, we found that ectopic expression of p300 increased endogenous IL-5 mRNA expression. Thus, the histone acetyltransferase (HAT) activity of CBP/p300 was required to activate IL-5 expression. This report provided evidence, for the first time, that CBP/p300 was involved in IL-5 gene expression and the HAT activity was important in regulation of IL-5 expression.
机译：白细胞介素5（IL-5）在嗜酸性粒细胞的生长和分化中起着核心作用，并导致包括哮喘在内的多种疾病。鉴定控制该细胞因子合成的转录机制引起了极大的兴趣。 IL-5信息的调节主要在转录水平上，并且很可能在很大程度上受启动子区域中可能影响基因转录活性的调节元件所控制。在这项研究中，我们用IL-5启动子-报告基因基因构建体和E1A（CBP / p300抑制剂或CBP / p300结合缺陷E1ADelta2-36的表达质粒）进行了一系列瞬时转染实验。结果表明，E1A抑制IL-5启动子活性，而E1ADelta2-36对其没有影响。这表明CBP / p300参与了IL-5基因表达的调节。转录共激活因子CBP / p300和转录因子C / EBP，NF-AT和c-Fossynergistic激活的IL-5启动子。此外，我们发现异位表达的p300增加内源性IL-5 mRNA表达。因此，需要CBP / p300的组蛋白乙酰转移酶（HAT）活性来激活IL-5表达。该报告首次提供证据，表明CBP / p300参与IL-5基因表达，而HAT活性在调节IL-5表达中很重要。

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