Abstract
BackgroundIndependent lines of evidence suggested that a large fraction of human genes possess multiple promoters driving gene expression from distinct transcription start sites. Understanding which promoter is employed in which cellular context is required to unravel gene regulatory networks within the cell.ResultsWe have developed a custom microarray platform that tiles roughly 35,000 alternative putative promoters from nearly 7,000 genes in the human genome. To demonstrate the utility of this array platform, we have analyzed the patterns of promoter usage in 17β-estradiol (E2)-treated and untreated MCF7 cells and show widespread usage of alternative promoters. Most intriguingly, we show that the downstream promoter in E2-sensitive multiple promoter genes tends to be very close to the 3'-terminus of the gene, suggesting exotic mechanisms of expression regulation in these genes.ConclusionThe usage of alternative promoters greatly multiplies the transcriptional complexity available within the human genome. The fact that many of these promoters are incapable of driving the synthesis of a meaningful protein-encoding transcript further complicates the story.
Highlights
Independent lines of evidence suggested that a large fraction of human genes possess multiple promoters driving gene expression from distinct transcription start sites
RNA polymerase II Chromatin Immunoprecipitation (ChIP)-chip as we have shown in this paper, but it is suitable for methylation based studies using DMH or meDIP experiments, or for ChIP-chip experiments using other proteins of interest, such as transcription factors or histone modification signatures
These results suggest that a large fraction of genes in the human genome possess undiscovered promoters and transcription start sites, which agrees with findings based on the mapping of expressed sequence tags (ESTs) to the genome [20,21], and the mapping of 5' oligo cap cDNA libraries to the genome [4]
Summary
Independent lines of evidence suggested that a large fraction of human genes possess multiple promoters driving gene expression from distinct transcription start sites. The regulation of human gene expression is known to be an extraordinarily complex process, including transcription, mRNA processing, mRNA transport, mRNA stability, mRNA translation, protein modification and protein stability. Genes with more than one promoter have been known for some time [2], and recent studies using independent lines of evidence have suggested that a large proportion of the human genome is transcribed from both strands [3] and numerous human genes have more than one promoter allowing gene transcription in different cellular conditions [4,5,6,7]. There are a significant number of single-promoter genes on the array, but these are invariably share a bidirectional promoter with multi-promoter genes
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