Research article

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

Gregory AC Singer^{* 1} , Jiejun Wu^{* 1,2} , Pearlly Yan^1,2 , Christoph Plass^1,2,3 , Tim HM Huang¹ and Ramana V Davuluri^1,4

¹Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH, USA

²Department of Molecular Genetics, The Ohio State University, Columbus, OH, USA

³German Cancer Research Center (DKFZ), Heidelberg, Germany

⁴Center for Systems and Computational Biology, Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA

author email corresponding author email* Contributed equally

BMC Genomics 2008, 9:349doi:10.1186/1471-2164-9-349

Published:	25 July 2008

Abstract

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 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.

Conclusion

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.