Promoter features related to tissue specificity as measured by Shannon entropy.

Promoter features related to tissue specificity as measured by Shannon entropy.
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DOI:
10.1186/gb-2005-6-4-r33
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发表时间:
2005
期刊:
影响因子:
12.3
通讯作者:
Stoeckert CJ Jr
Stoeckert CJ Jr
中科院分区:
生物学1区
文献类型:
--
作者:
Schug J;Schuller WP;Kappen C;Salbaum JM;Bucan M;Stoeckert CJ Jr

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启动子的全基因组分析是在使用人类微阵列和基于EST的表达数据的组织调查中的基因表达模式的背景下进行的。该研究揭示,大多数基因表现出统计学上显著的表达水平的组织依赖性变化,并鉴定了区分组织特异性基因和普遍存在的基因的启动子组分。组织特异性的调节机制是多细胞生物体发育和维持的关键部分。在组织调查的基因表达模式的背景下,启动子的全基因组分析提供了一种确定这些机制的一般原则的方法。我们引入了基于香农熵的组织特异性的定义,根据其整体组织特异性和对特定组织的特异性对人类基因进行排名。我们将我们的定义应用于基于微阵列和基于表达序列标签(EST)的人类基因表达数据,并使用小鼠基因的类似数据来验证我们的结果。我们发现,大多数基因的表达水平表现出统计学显著的组织依赖性变化。我们发现大多数组织特异性基因通常具有TATA盒,没有CpG岛,并且通常编码细胞外蛋白。正如预期的那样,CpG岛存在于大多数组织特异性最低的基因中,这些基因通常编码位于细胞核或细胞核中的蛋白质。没有CpG岛或TATA盒的基因是最常见的中特异性基因,通常编码位于膜上的蛋白质。发现Sp1是较低特异性表达的弱指标。YY1结合位点,无论是作为启动子或作为下游位点,都与特异性最低的基因密切相关。我们已经开始了解区分组织特异性基因和普遍存在的基因的启动子的组成部分,以确定仅从序列数据就可以预测广泛类别的基因表达的关联。
A genome-wide analysis of promoters was carried out in the context of gene expression patterns in tissue surveys using human microarray and EST-based expression data. The study revealed that most genes show statistically significant tissue-dependent variations of expression level and identified components of promoters that distinguish tissue-specific from ubiquitous genes. The regulatory mechanisms underlying tissue specificity are a crucial part of the development and maintenance of multicellular organisms. A genome-wide analysis of promoters in the context of gene-expression patterns in tissue surveys provides a means of identifying the general principles for these mechanisms. We introduce a definition of tissue specificity based on Shannon entropy to rank human genes according to their overall tissue specificity and by their specificity to particular tissues. We apply our definition to microarray-based and expressed sequence tag (EST)-based expression data for human genes and use similar data for mouse genes to validate our results. We show that most genes show statistically significant tissue-dependent variations in expression level. We find that the most tissue-specific genes typically have a TATA box, no CpG island, and often code for extracellular proteins. As expected, CpG islands are found in most of the least tissue-specific genes, which often code for proteins located in the nucleus or mitochondrion. The class of genes with no CpG island or TATA box are the most common mid-specificity genes and commonly code for proteins located in a membrane. Sp1 was found to be a weak indicator of less-specific expression. YY1 binding sites, either as initiators or as downstream sites, were strongly associated with the least-specific genes. We have begun to understand the components of promoters that distinguish tissue-specific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone.
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