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首页> 外文期刊>PLoS Genetics >Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels
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Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels

机译：定量遗传分析Deciphers CIS和反式调节对蛋白质表达水平细胞对细胞变异性的影响

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Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis . However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans , with notably fewer variants acting in cis . Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans .
机译：鉴定复杂多细胞生物中的蛋白质表达变异性的因素主要集中在顺式中的启动子结构和单细胞表达的调节。然而，这种有针对性的方法必须迄今为止无法识别人类细胞对细胞基因表达变异性的主要调节因子。为了解决这一点，我们使用具有定量遗传学分析的流式细胞术来组合在人免疫系统中的单细胞蛋白表达测量。对于大多数蛋白质的表达可变性具有遗传性成分，我们发现遗传变异在反式中起作用，显着较少在顺式中作用的变体。此外，我们突出了孟德尔随机化，即这些可变性定量特性基因座可能由上游基因的CIS调节驱动。这表明自然选择可以平衡CIS在CIS中的影响与反式表达变异性的下游影响。

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