Barriers to transmission of transcriptional noise in a c-fos c-jun pathway
Barriers to transmission of transcriptional noise in a c-fos c-jun pathway
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DOI：
10.1038/msb.2013.45
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发表时间：
2013-09-01
影响因子：
9.9
通讯作者：
Tyagi, Sanjay
中科院分区：
文献类型：
--
作者：
Shah, Khyati;Tyagi, Sanjay
我们通过研究转录因子c-fos和c-jun对两个下游基因的诱导作用来探讨转录噪音在基因调控通路中的传播，这两个转录因子在血清刺激细胞后产生短暂的时间，然后通过与靶基因的启动子结合形成异二聚体来激活它们。我们发现，即使它们在群体水平上协调表达，在单个细胞中，c-fos和c-jun的表达是嘈杂的，彼此不相关。下游基因的表达也有噪音，但上游基因的噪音对下游基因的表达影响很小或没有影响。噪声不会被传递，因为单个细胞中存在的异源二聚体的数量相对不变，并且下游基因的诱导对单个细胞中异源二聚体的数量不敏感。紧密染色质内下游基因的启动子的隔离是这种不敏感性的可能原因。这些对噪音传播和放大的障碍在高等真核生物中可能是常见的。
We explored how transcriptional noise propagates in gene-regulatory pathways by studying the induction of two downstream genes by transcription factors c-fos and c-jun. They are produced for a brief period following serum stimulation of cells and then activate the promoters of their target genes by binding to them as heterodimers. We found that, even though they are coordinately expressed at the population level, in individual cells the expression of c-fos and c-jun is noisy and uncorrelated with each other. The expression of the downstream genes is also noisy, but there is little or no effect of the noise in the upstream genes on the expression of the downstream genes. The noise is not transmitted, because the number of heterodimers present in single cells is relatively invariant, and the induction of downstream genes is insensitive to the number of heterodimers in individual cells. Sequestration of promoters of the downstream genes within compact chromatin is a likely cause of this insensitivity. These barriers to the propagation and amplification of noise are likely to be commonplace in higher eukaryotes.