Plasticity of the cis-regulatory input function of a gene.
Plasticity of the cis-regulatory input function of a gene.
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DOI：
10.1371/journal.pbio.0040045
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发表时间：
2006-04
期刊：
影响因子：
9.8
通讯作者：
Alon U
中科院分区：
文献类型：
--
作者：
Mayo AE;Setty Y;Shavit S;Zaslaver A;Alon U
基因的转录速率通常由几个结合基因顺式调控区域特定位点的调控因子控制。这些调节因子的综合作用用顺式调节输入函数来描述。什么决定了输入函数的形式，以及它相对于突变有多可变？为了解决这个问题，我们采用了大肠杆菌的lac操纵子，它具有复杂的输入函数，介于布尔与门和或门逻辑之间。通过对活细胞的精确表达测量，我们详细绘制了lac启动子的12个变体的输入函数，每个变体在调节因子结合位点上具有不同的点突变。我们发现，即使是少数突变也能显著改变输入函数，从而产生类似于纯与门、或门或单输入开关的函数。其他类型的门没有被发现。不同的输入函数可以用数学模型统一描述。该模型还可以让我们预测哪些功能不能通过点突变达到。因此，我们研究的输入函数似乎是可塑的，从某种意义上说，许多突变并没有完全破坏调控，而是产生了整合输入的新方法。大肠杆菌lac操纵子的几个点突变足以改变转录计算的性质。
The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each with different point mutations in the regulator binding sites, by means of accurate expression measurements from living cells. We find that even a few mutations can significantly change the input function, resulting in functions that resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs. A few point mutations in the lac operon of Escherichia coli are sufficient to change the nature of the transcriptional computation.
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影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
64.8
作者：
Dekel, E;Alon, U
通讯作者：
Alon, U
影响因子：
2
作者：
GLASS, L;KAUFFMAN, SA
通讯作者：
KAUFFMAN, SA
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R
DOI：
10.1073/pnas.0307571101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Basu, S;Mehreja, R;Weiss, R
通讯作者：
Weiss, R