Positive feedback in eukaryotic gene networks:: cell differentiation by graded to binary response conversion
Positive feedback in eukaryotic gene networks:: cell differentiation by graded to binary response conversion
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DOI：
10.1093/emboj/20.10.2528
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发表时间：
2001-05-15
期刊：
影响因子：
11.4
通讯作者：
Serrano, L
中科院分区：
文献类型：
--
作者：
Becskei, A;Séraphin, B;Serrano, L
反馈是基因网络中普遍存在的一种控制机制。在此，我们利用正反馈在酿酒酵母中构建了一个合成的真核基因开关，在这个系统中，当激活子被自催化表达时，连续梯度的组成表达转录激活子被翻译成细胞表型开关。这一发现与数学模型相一致，该模型的分析表明，连续输入参数通过正反馈转换为双峰概率分布，这类似于模拟-数字转换。自催化开关是真核生物基因表达的一个重要特性。虽然群体中单个细胞的行为是随机的，但显示低或高表达状态的细胞群体的比例是可以调节的。这些结果对理解增强剂作用和细胞分化的分级和概率机制具有重要意义。
Feedback is a ubiquitous control mechanism of gene networks. Here, we have used positive feedback to construct a synthetic eukaryotic gene switch in Saccharomyces cerevisiae, Within this system, a continuous gradient of constitutively expressed transcriptional activator is translated into a cell phenotype switch when the activator is expressed autocatalytically. This finding is consistent with a mathematical model whose analysis shows that continuous input parameters are converted into a bimodal probability distribution by positive feedback, and that this resembles analog-digital conversion. The autocatalytic switch is a robust property in eukaryotic gene expression. Although the behavior of individual cells within a population is random, the proportion of the cell population displaying either low or high expression states can be regulated. These results have implications for understanding the graded and probabilistic mechanisms of enhancer action and cell differentiation.