Abstract Altered levels of histone acetylation are associated with changes in chromosomal gene expression. Thus, the specific acetylation of histones bound to plasmid DNA might increase transgene expression. Previously, the expression of the histone acetyltransferase domain of CREB-binding protein fused to the sequence-dependent DNA binding domain of GAL4 (GAL4-HAT) successfully improved reporter gene expression in cultured cells [J. Biosci. Bioengng. 123, 277–280 (2017)]. In this study, the same approach was applied for transgene expression in mice. The activator and reporter plasmid DNAs bearing the genes for GAL4-HAT and Gaussia princeps luciferase, respectively, were co-administered into the mouse liver by hydrodynamics-based tail vein injection, and the Gaussia luciferase activity in serum was measured for two weeks. Unexpectedly, the co-injection of the GAL4-HAT and luciferase plasmid DNAs seemed to decrease, rather than increase, luciferase expression. Moreover, the co-injection apparently reduced the amount of luciferase DNA in the liver. These results indicated that this system is ineffective in vivo and suggested the exclusion of hepatic cells expressing GAL4-HAT.

中文翻译：

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质粒特异性组蛋白乙酰转移酶募集系统对体内转基因表达无增强作用

摘要 组蛋白乙酰化水平的改变与染色体基因表达的变化有关。因此，与质粒 DNA 结合的组蛋白的特定乙酰化可能会增加转基因表达。以前，CREB ​​结合蛋白的组蛋白乙酰转移酶结构域与 GAL4 的序列依赖性 DNA 结合结构域 (GAL4-HAT) 的表达成功地提高了培养细胞中报告基因的表达 [J. 生物科学。生物工程。123, 277–280 (2017)]。在这项研究中，相同的方法应用于小鼠的转基因表达。通过基于流体动力学的尾静脉注射将分别带有 GAL4-HAT 和 Gaussia Princeps 荧光素酶基因的激活剂和报告基因质粒 DNA 共同给药到小鼠肝脏中，并测量血清中 Gaussia 荧光素酶活性两周。不料，GAL4-HAT 和荧光素酶质粒 DNA 的共同注射似乎降低了，而不是增加了荧光素酶的表达。此外，联合注射明显减少了肝脏中荧光素酶 DNA 的数量。这些结果表明该系统在体内无效，并表明排除了表达 GAL4-HAT 的肝细胞。