Programming gene expression with combinatorial promoters.
Programming gene expression with combinatorial promoters.
复制标题
用组合启动子编程基因表达。
DOI：
10.1038/msb4100187
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发表时间：
2007
影响因子：
9.9
通讯作者：
Elowitz, Michael B
中科院分区：
文献类型：
--
作者：
Cox, Robert Sidney 3rd;Surette, Michael G;Elowitz, Michael B
启动子响应一种或多种转录因子（TFs）来控制基因的表达。启动子的结构是指其内部结合位点的排列和类型。为了理解天然的基因回路以及为合成生物学设计启动子，理解启动子功能和结构之间的关系至关重要。我们构建了一个随机启动子结构的组合文库。我们对大肠杆菌中的288个启动子进行了表征，每个启动子包含来自四种不同转录因子的多达三个输入。文库设计允许存在多个-10区和-35区，并且我们观察到启动子强度在五个数量级上有所不同。为了进一步分析功能库，我们从调控范围、逻辑类型和对称性方面定义了启动子功能的一种表示形式。利用这些结果，我们确定了用组合启动子对基因表达进行编程的启发式规则。
Promoters control the expression of genes in response to one or more transcription factors (TFs). The architecture of a promoter is the arrangement and type of binding sites within it. To understand natural genetic circuits and to design promoters for synthetic biology, it is essential to understand the relationship between promoter function and architecture. We constructed a combinatorial library of random promoter architectures. We characterized 288 promoters in Escherichia coli, each containing up to three inputs from four different TFs. The library design allowed for multiple −10 and −35 boxes, and we observed varied promoter strength over five decades. To further analyze the functional repertoire, we defined a representation of promoter function in terms of regulatory range, logic type, and symmetry. Using these results, we identified heuristic rules for programming gene expression with combinatorial promoters.