Promoter features related to tissue specificity as measured by Shannon entropy

By Jonathan Schug, Winfried Schuller, Claudia Kappen, J. Michael Salbaum, Maja Bucan, Christian J. Stoeckert Jr.. Genome Biology, 2005

464 citations recorded by the source corpus.

BackgroundThe 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.ResultsWe 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.ConclusionsWe 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7e9aa0fba59db63cd416297b1e2ed165b6f42d84

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In Molecular Biology

Citations in the corpus

Epigenomic Analysis of Multi-lineage Differentiation of Human Embryonic Stem Cells (2013, unknown): “Using an entropy-basedmethod (Barrera et al., 2008; Schug et al., 2005) (Figure S2B), we identified 2,408 genes that showed cell-type-specific expression (Figures 2A and S2A).”
A benchmark of gene expression tissue-specificity metrics (2015, methodology): “…specificity index TSI (Julien et al. 2012) (used in e.g. (Cortez et al. 2014; Assis & Bachtrog 2015; Winter et al. 2004)); Hg by Schug et al. (Schug et al. 2005); the z-score (used in (Vandenbon & Nakai 2010)), widely used for other features than tissue specificity; SPM, used in the database…”
Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. (2006, background): “(E) Tissue specificity of promoter-methylated, body-methylated, and unmethylated genes measured by entropy level (Schug et al., 2005).”
Genome-wide analysis of mammalian promoter architecture and evolution (2006, background): “In general, ubiquitous transcripts were associated with a broad TSS and CpG islands, whereas tightly regulated transcripts were associated with sharper distinct TSSs and TATA-box promoter”
Whole-Genome Analysis of Histone H3 Lysine 27 Trimethylation in Arabidopsis (2007, background): “Importantly, most H3K27me3 target genes are expressed in a very tissue-specific manner (Figure 2B), as measured by Shannon entropy [36], suggesting that H3K27me3 may facilitate the repression of these genes in appropriate tissues.”