Promoter features related to tissue specificity as measured by Shannon entropy

Jonathan Schug¹ , Winfried-Paul Schuller², Claudia Kappen², J Michael Salbaum², Maja Bucan³ and Christian J Stoeckert Jr¹

¹Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, USA

²Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA

³Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA

author email corresponding author email

Genome Biology 2005, 6:R33doi:10.1186/gb-2005-6-4-r33


Published:	29 March 2005

Subject areas: Molecular biology, Bioinformatics, Genetics, Genome studies

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 tissue-specific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone.