In silico identification of transcriptional regulators associated with c-Myc

Nucleic Acids Research
Ran ElkonYosef Shiloh

Abstract

The development of powerful experimental strategies for functional genomics and accompanying computational tools has brought major advances in the delineation of transcriptional networks in organisms ranging from yeast to human. Regulation of transcription of eukaryotic genes is to a large extent combinatorial. Here, we used an in silico approach to identify transcription factors (TFs) that form recurring regulatory modules with c-Myc, a protein encoded by an oncogene that is frequently disregulated in human malignancies. A recent study identified, on a genomic scale, human genes whose promoters are bound by c-Myc and its heterodimer partner Max in Burkitt's lymphoma cells. Using computational methods, we identified nine TFs whose binding-site signatures are highly overrepresented in this promoter set of c-Myc targets, pointing to possible functional links between these TFs and c-Myc. Binding sites of most of these TFs are also enriched on the set of mouse homolog promoters, suggesting functional conservation. Among the enriched TFs, there are several regulators known to control cell cycle progression. Another TF in this set, EGR-1, is rapidly activated by numerous stress challenges and plays a central role in angiogenesis. Exp...Continue Reading

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Citations

Jul 1, 2005·Molecular and Cellular Biology·Feng LiChi V Dang
May 2, 2012·The Journal of Clinical Investigation·Elaine Y ChungAndrei Thomas-Tikhonenko
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kenneth R RogulskiEdward V Prochownik
Jun 14, 2005·Current Opinion in Genetics & Development·Tanya Vavouri, Greg Elgar
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Nov 3, 2007·Experimental Neurology·Yaniv AssafAri Barzilai
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