Transcriptional Amplification in Tumor Cells with Elevated c-Myc
Name
Burge_Transcriptional amplification.pdf
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2.76 MB
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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.
Date Issued
September 2012
Journal
Cell
Publisher
Elsevier B.V.
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2012.08.026
