Zhong, Sheng;Wong, Wing Hung - Prediction of transcription factors that activate promoters with E2F in a synergistic manner

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Title: Prediction of transcription factors that activate promoters with E2F in a synergistic manner	P188
Zhong, Sheng; Wong, Wing Hung szhong@hsph.harvard.edu Department of Biostatistics, School of Public Health, Harvard University

The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators1. However, it has been shown that the presence of an E2F site is not sufficient for G1/S phase transcriptional regulation. Some transcription factors can interact with E2F and activate promoters in a synergistic manner. Such interactions stabilize DNA binding and contribute to promoter-specificity2,3. Here we describe a computational prediction method for transcription factors that may cooperate with E2F.

First, we selected a large set of control promoters. We used all available weight matrices on TRANSFAC to scan the control promoters, and recorded the distribution of the scan hits. Second, we scanned the promoters of E2F target genes, and identified significant clusters of putative binding sites for every single transcription factor. The transcriptions factors that have clustered putative binding sites on more than one promoter are selected. At last we cross checked human and mouse promoters. A transcription factor is given a higher rank in prediction, if its binding site clusters are significant in the promoters of homolog E2F target genes in both human and mouse.

Through literature search, we totally found 5 transcription factors that activate promoters together with E2F in a synergistic manner2,3. All of the 5 transcription factors are among the top 8 predictions.

[1] Trimarchi, J. M. & Lees, J. A. Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3, 11-20 (2002).
[2] van Ginkel, P. R., Hsiao, K. M., Schjerven, H. & Farnham, P. J. E2F-mediated growth regulation requires transcription factor cooperation. J Biol Chem 272, 18367-74 (1997).
[3] Rotheneder, H., Geymayer, S. & Haidweger, E. Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter. J Mol Biol 293, 1005-15 (1999).