What are the determinants of gene expression levels and breadths in the human genome?
What are the determinants of gene expression levels and breadths in the human genome?
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DOI：
10.1093/hmg/ddr436
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发表时间：
2012-01-01
影响因子：
3.5
通讯作者：
Yi SV
中科院分区：
文献类型：
--
作者：
Park J;Xu K;Park T;Yi SV
在复杂的生物体中，不同的组织表达不同的基因，这些基因最终塑造了每个组织的功能和表型。现代生物学的一个重要目标是了解某些基因在特定组织中是如何开启和关闭的，以及不同基因表达产物的数量是如何确定的。这些方面分别称为“表达宽度”（或“组织特异性”）和“表达水平”。在这里，我们表明，我们可以预测大量的变化水平和宽度的基因表达使用每个基因的基因组信息。有趣的是，许多基因组性状与基因表达的两个方面在相似的方向上相关，表明共享的分子途径。然而，为了阐明不同的分子机制，基因表达水平和宽度，我们需要确定这两个方面的基因表达的基因组性状的相对意义。为此，我们开发了一种新的多元多元回归方法。使用这种新的方法，我们表明，基因的紧凑性（特别是，外显子的平均大小），密码子使用的偏见和非同义率有更强的影响表达水平相比，他们对表达宽度的影响。相比之下，启动子DNA甲基化的倾向是表达宽度比表达水平更强的指标。有趣的是，内含子DNA甲基化在人类基因组中表现出与启动子DNA甲基化相反的模式，这表明DNA甲基化可能根据其基因组靶点发挥多种作用。此外，同义率与人类基因组中的表达宽度比与表达水平具有更强的关联。这些发现为调节基因表达不同方面的独特分子机制提供了线索。
In complex organisms, different tissues express different genes, which ultimately shape the function and phenotype of each tissue. An important goal of modern biology is to understand how some genes are turned on and off in specific tissues and how the numbers of different gene expression products are determined. These aspects are named ‘expression breadth’ (or ‘tissue specificity’) and ‘expression level’, respectively. Here, we show that we can predict substantial amount of variation in levels and breadths of gene expression using genomic information of each gene. Interestingly, many genomic traits are correlated with both aspects of gene expression in similar directions, suggesting shared molecular pathways. However, to elucidate distinctive molecular mechanisms governing gene expression levels and breadths, we need to identify the relative significance of each genomic trait on these two aspects of gene expression. To this end, we developed a novel multivariate multiple regression method. Using this new method, we show that gene compactness (in particular, the mean size of exons), codon usage bias and non-synonymous rates have a stronger influence on expression levels compared with their effects on expression breadths. In contrast, the propensity of promoter DNA methylation is a stronger indicator of expression breadths than of expression levels. Interestingly, intron DNA methylation exhibits an opposite pattern to the promoter DNA methylation in the human genome, suggesting that DNA methylation may play multiple roles depending upon its genomic targets. Furthermore, synonymous rates have stronger associations with expression breadths than with expression levels in the human genome. These findings provide clues toward distinctive molecular mechanisms regulating different aspects of gene expression.
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