Abstract
BackgroundThe purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene.ResultsUsing ProSpector, a web-based promoter search and annotation tool, we have applied an unbiased approach to analyze the transcription factor binding site frequencies of 1400 base pair genomic segments positioned at 1200 base pairs upstream and 200 base pairs downstream of the transcriptional start site of 7298 commonly studied human genes. Partitional clustering of the transcription factor binding site composition within these promoter segments reveals a small number of gene groups that are selectively enriched for gene ontology terms consistent with distinct aspects of cellular function. Significance ranking of the class-determining transcription factor binding sites within these clusters show substantial overlap between the gene ontology terms of the transcriptions factors associated with the binding sites and the gene ontology terms of the regulated genes within each group.ConclusionThus, gene sorting by promoter composition alone produces partitions in which the "regulated" and the "regulators" cosegregate into similar functional classes. These findings demonstrate that the transcription factor binding site composition is non-randomly distributed between gene promoters in a manner that reflects and partially defines general gene class function.
Highlights
The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene
CFilguustreer 1analysis of gene expression data set from mitogen stimulated T-cells compared to promoter TFBS composition Cluster analysis of gene expression data set from mitogen stimulated T-cells compared to promoter TFBS composition. (a) K-means cluster analysis of cDNA expression profiles of phorbol ester and ionomycin stimulated Jurkat Tcells collected at 0, 1, 2, 6, 12, and 24 hours after stimulation [11]
Total genes in each cluster is indicated in parentheses. (b) Centroid plot representing average kinetic profiles of the four clusters at the six measured time intervals. (c) Principal component analysis (PCA) of TFBS frequencies in the genomic sequences extracted from the 7,298 genes profiled in Figure 1a. (1200 base pairs upstream and 200 base pairs down stream from the start of transcription)
Summary
The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene. The search, retrieval and examination of the upstream regulatory sequences of eukaryotic genes coupled with empirical determination of their transcriptional regulatory function has yielded a wealth of potentially useful information relevant to the sequencespecific codes used to dynamically coordinate the spatial, temporal, and kinetic assembly of gene regulatory complexes at specific genes [1]. Cells must orchestrate this coordinated gene expression in order to efficiently execute the multitude of cellular programs that direct specific functions. Focused and global analysis of gene promoter composition has the potential of yielding important insight into gene regulation
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