No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo |
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Authors: | Tetsuya Suzuki Yusuke Wakao Tadashi Watanabe Mika Hori Yoshito Ikeda Hiroyuki Tsuchiya |
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Institution: | 1. Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan;2. Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, Japan;3. Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan;4. Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan;5. Laboratory of Medicinal Cell Biology, Kobe Pharmaceutical University, Kobe, Japan;6. Graduate School of Medicine, Tottori University, Yonago, Tottori, Japan |
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Abstract: | AbstractAltered 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. |
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Keywords: | Histone acetyltransferase plasmid DNA transgene expression |
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