Genome-wide analysis of alternative promoters of human genes using a custom promoter tiling array.
BACKGROUND
Independent 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.


RESULTS
We 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 17beta-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.


CONCLUSIONS
The 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.
Singer
Gregory A C
GA
Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH, USA. gacsinger@gmail.com
Wu
Jiejun
J
Yan
Pearlly
P
Plass
Christoph
C
Huang
Tim H M
TH
Davuluri
Ramana V
RV
D045744:Cell Line, Tumor; D018899:CpG Islands; D015342:DNA Probes; D004958:Estradiol / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024363:Transcription Initiation Site
D015342:DNA Probes; D004958:Estradiol; D012319:RNA Polymerase II