Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication
Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication
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DOI：
10.1073/pnas.1800943115
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发表时间：
2018-08-14
影响因子：
11.1
通讯作者：
Chubb, Jonathan R.
中科院分区：
文献类型：
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作者：
Tunnacliffe, Edward;Corrigan, Adam M.;Chubb, Jonathan R.
在基因家族的进化过程中，蛋白质的功能多样化往往伴随着基因复制。然而，许多基因家族在保留蛋白质序列的同时扩展。为什么细胞会保持同一基因的多个拷贝？在这里，我们已经解决了这个问题，肌动蛋白家族有17个基因编码相同的蛋白质。这些基因有不同的侧翼区域，分散在整个基因组中。令人惊讶的是，几乎整个家族都表现出相似的发育表达谱，它们的表达在单个细胞中也强烈偶联。利用活细胞成像，我们发现基因表达的差异在较短的时间尺度上是明显的，家庭成员表现出不同的转录爆发动力学。强烈的“爆发”行为与稳定的、更持续的活动形成对比，表明个体肌动蛋白基因的不同调控输入。为了确定这些不同动态行为的来源，我们相互交换了基因家族成员的上游调控区域。这表明动态转录行为是由上游序列直接指示的，而不是特定于基因组背景的特征。基因组环境的一个残余的微小贡献调节了基因的OFF率。我们的数据表明，基因复制后启动子的多样化可以扩大调节必需基因表达的刺激范围。这些观察结果说明了转录爆发的重要性。
During the evolution of gene families, functional diversification of proteins often follows gene duplication. However, many gene families expand while preserving protein sequence. Why do cells maintain multiple copies of the same gene? Here we have addressed this question for an actin family with 17 genes encoding an identical protein. The genes have divergent flanking regions and are scattered throughout the genome. Surprisingly, almost the entire family showed similar developmental expression profiles, with their expression also strongly coupled in single cells. Using live cell imaging, we show that differences in gene expression were apparent over shorter timescales, with family members displaying different transcriptional bursting dynamics. Strong "bursty" behaviors contrasted steady, more continuous activity, indicating different regulatory inputs to individual actin genes. To determine the sources of these different dynamic behaviors, we reciprocally exchanged the upstream regulatory regions of gene family members. This revealed that dynamic transcriptional behavior is directly instructed by upstream sequence, rather than features specific to genomic context. A residual minor contribution of genomic context modulates the gene OFF rate. Our data suggest promoter diversification following gene duplication could expand the range of stimuli that regulate the expression of essential genes. These observations contextualize the significance of transcriptional bursting.