Transcriptional Amplification in Tumor Cells with Elevated c-Myc
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2014
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| Online Access: | http://hdl.handle.net/1721.1/83614 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1811083591866646528 |
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| author | Lin, Charles Y. Loven, Jakob Rahl, Peter B. Paranal, Ronald M. Burge, Christopher B. Bradner, James E. Lee, Tong Ihn Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Lin, Charles Y. Loven, Jakob Rahl, Peter B. Paranal, Ronald M. Burge, Christopher B. Bradner, James E. Lee, Tong Ihn Young, Richard A. |
| author_sort | Lin, Charles Y. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:35:31Z |
| format | Article |
| id | mit-1721.1/83614 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:35:31Z |
| publishDate | 2014 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/836142022-09-28T08:51:26Z Transcriptional Amplification in Tumor Cells with Elevated c-Myc Lin, Charles Y. Loven, Jakob Rahl, Peter B. Paranal, Ronald M. Burge, Christopher B. Bradner, James E. Lee, Tong Ihn Young, Richard A. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lin, Charles Y. Loven, Jakob Rahl, Peter B. Burge, Christopher B. Lee, Tong Ihn Young, Richard A. 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. National Institutes of Health (U.S.) (grant HG002668) National Institutes of Health (U.S.) (grant CA14644) Swedish Research Council Swedish Research Council (Postdoctoral Fellowship, VR-B008630) American Cancer Society (Postdoctoral Fellowship PF-11- 042- 01-DMC) Damon Runyon Cancer Research Foundation 2014-01-08T20:58:12Z 2014-01-08T20:58:12Z 2012-09 2012-05 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/83614 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. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.cell.2012.08.026 Cell 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. application/pdf Elsevier B.V. Elsevier Open Archive |
| spellingShingle | Lin, Charles Y. Loven, Jakob Rahl, Peter B. Paranal, Ronald M. Burge, Christopher B. Bradner, James E. Lee, Tong Ihn Young, Richard A. Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title | Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title_full | Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title_fullStr | Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title_full_unstemmed | Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title_short | Transcriptional Amplification in Tumor Cells with Elevated c-Myc |
| title_sort | transcriptional amplification in tumor cells with elevated c myc |
| url | http://hdl.handle.net/1721.1/83614 https://orcid.org/0000-0001-8855-8647 |
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