Transcriptional Amplification in Tumor Cells with Elevated c-Myc
Author(s)Lin, Charles Y.; Loven, Jakob; Rahl, Peter B.; Paranal, Ronald M.; Burge, Christopher B.; Bradner, James E.; Lee, Tong Ihn; Young, Richard A.; ... Show more Show less
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Elevated expression of the c-Myc transcription factor occurs frequently in human cancers and is associated with tumor aggression and poor clinical outcome. The effect of high levels of c-Myc on global gene regulation is poorly understood but is widely thought to involve newly activated or repressed “Myc target genes.” We report here that in tumor cells expressing high levels of c-Myc the transcription factor accumulates in the promoter regions of active genes and causes transcriptional amplification, producing increased levels of transcripts within the cell’s gene expression program. Thus, rather than binding and regulating a new set of genes, c-Myc amplifies the output of the existing gene expression program. These results provide an explanation for the diverse effects of oncogenic c-Myc on gene expression in different tumor cells and suggest that transcriptional amplification reduces rate-limiting constraints for tumor cell growth and proliferation.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Lin, Charles Y., Jakob Loven, Peter B. Rahl, Ronald M. Paranal, Christopher B. Burge, James E. Bradner, Tong Ihn Lee, and Richard A. Young. “Transcriptional Amplification in Tumor Cells with Elevated c-Myc.” Cell 151, no. 1 (September 2012): 56-67. © 2012 Elsevier Inc.
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