An engineered epigenetic transgene switch in mammalian cells
An engineered epigenetic transgene switch in mammalian cells
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DOI：
10.1038/nbt980
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发表时间：
2004-07-01
影响因子：
46.9
通讯作者：
Fussenegger, M
中科院分区：
文献类型：
--
作者：
Kramer, BP;Viretta, AU;Fussenegger, M
在多细胞系统中，细胞身份是由表观遗传调控回路印记的，表观遗传调控回路以细胞表型特异性方式决定成体细胞的整体转录组（1-3）。通过结合两个抑制剂，控制对方的表达，我们已经开发出一种哺乳动物的表观遗传电路能够在两个稳定的转基因表达状态之间切换后，短暂的两种替代药物的管理。工程化的中国仓鼠卵巢细胞（CHO-K1）在培养中以及微囊化和植入小鼠后显示出人类糖蛋白的切换开关特异性表达谱。开关动力学和表达稳定性可以用数学模型预测。通过拨动开关进行表观遗传转基因控制是在哺乳动物细胞中工程化人工基因网络的重要工具。
In multicellular systems cell identity is imprinted by epigenetic regulation circuits, which determine the global transcriptome of adult cells in a cell phenotype-specific manner(1-3). By combining two repressors, which control each other's expression, we have developed a mammalian epigenetic circuitry able to switch between two stable transgene expression states after transient administration of two alternate drugs. Engineered Chinese hamster ovary cells (CHO-K1) showed toggle switch-specific expression profiles of a human glycoprotein in culture, as well as after microencapsulation and implantation into mice. Switch dynamics and expression stability could be predicted with mathematical models. Epigenetic transgene control through toggle switches is an important tool for engineering artificial gene networks in mammalian cells.