TY  - JOUR
A1  - Bieda, Mark
A1  - Xu, Xiaoqin
A1  - Singer, Michael A.
A1  - Green, Roland
A1  - Farnham, Peggy J.
T1  - Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome
Y1  - 2006/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 595 
EP  - 605 
DO  - 10.1101/gr.4887606 
VL  - 16 
IS  - 5 
UR  - http://genome.cshlp.org/content/16/5/595.abstract 
N2  - The E2F family of transcription factors regulates basic cellular processes. Here, we take an unbiased approach towards identifying E2F1 target genes by examining localization of E2F1-binding sites using high-density oligonucleotide tiling arrays. To begin, we developed a statistically-based methodology for analysis of ChIP-chip data obtained from arrays that represent 30 Mb of the human genome. Using this methodology, we identified regions bound by E2F1, MYC, and RNA Polymerase II (POLR2A). We found a large number of binding sites for all three factors; extrapolation suggests there may be ∼20,000–30,000 E2F1- and MYC-binding sites and ∼12,000–17,000 active promoters in HeLa cells. In contrast to our results for MYC, we find that the majority of E2F1-binding sites (>80%) are located in core promoters and that 50% of the sites overlap transcription starts. Only a small fraction of E2F1 sites possess the canonical binding motif. Surprisingly, we found that ∼30% of genes in the 30-Mb region possessed an E2F1 binding site in a core promoter and E2F1 was bound near to 83% of POLR2A-bound sites. To determine if these results were representative of the entire human genome, we performed ChIP-chip analyses of ∼24,000 promoters and confirmed that greater than 20% of the promoters were bound by E2F1. Our results suggest that E2F1 is recruited to promoters via a method distinct from recognition of the known consensus site and point toward a new understanding of E2F1 as a factor that contributes to the regulation of a large fraction of human genes. 
ER  -