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Kinetic profiling of the c-Myc transcriptome and bioinformatic analysis of repressed gene promoters

Chui-Sun Yap, Abigail L. Peterson, Gastone Castellani, John M. Sedivy and Nicola Neretti

Myc is an oncogenic transcription factor whose expression is deregulated in many human cancers. It regulates a large proportion of the transcriptome with a small fold change and in both directions; including those involved in cell growth and the cell cycle. In order to better understand Myc’s biology, we profiled the transcriptome of rat fibroblasts before and after the induction of Myc activity. Approximately 20% of the transcriptome was regulated by Myc. Many of the upregulated genes are involved in anabolic processes, organelle biogenesis (e.g. mitochondria) and the cell cycle. However, a significant proportion of genes involved in the M phase was downregulated. The fine temporal resolution of the results enabled us to identify genes that were directly repressed by Myc. The mechanism of Myc repression had been shown to involve the interference of transactivation activities of other transcription factors. Hence we analyzed the promoters of the directly repressed genes to identify transcription factors that are mediate Myc transrepression. Putative factors include Ras responsive element binding protein 1 and myeloid zinc finger 1.

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