Promoter features related to tissue-specific expression

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.

Abstract Background: 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. Results: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. Conclusions:We have begun to understand the components of promoters that distinguish tissuespecific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone. BackgroundThe development of an adult from the single cell of a fertilized egg requires a complex orchestration of genes to be expressed at the right time, place, and level. Basic cellular functions require the expression of certain genes in all cells and tissues (that is, in a ubiquitous manner) while specialized functions require restricted expression of other genes in a single or small number of cells and tissues (that is, tissue specific). Both types of genes may be needed for embryonic development as well as for the function of adult cells and tissues. While the details of regulatory mechanisms will vary for individual genes, general features of promoters (and here we will restrict our focus to RNA polymerase II (Pol II) promoters) are likely to facilitate whether a gene will be expressed widely or in a restricted manner. For example, based on the limited number of genes available at the time of the analysis, promoters with CpG islands have been associated with h...