This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Weber, A.
Right arrow Articles by Levens, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weber, A.
Right arrow Articles by Levens, D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2005, p. 147-161, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.147-161.2005

TFIIH Operates through an Expanded Proximal Promoter To Fine-Tune c-myc Expression

Achim Weber,1,2,{dagger} Juhong Liu,1,{dagger} Irene Collins,1 and David Levens1*

Laboratory of Pathology, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland,1 Institute of Pathology, University of Mainz, Mainz, Germany2

Received 15 July 2004/ Returned for modification 12 August 2004/ Accepted 30 September 2004

A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor IIH (TFIIH) is held at promoters prior to promoter escape and so is well situated to channel the input of activators and repressors to modulate c-myc expression. We have compared cells expressing only a mutated p89 (xeroderma pigmentosum complementation group B [XPB]), the largest TFIIH subunit, with the same cells functionally complemented with the wild-type protein (XPB/wt-p89). Here, we show structural, compositional, and functional differences in transcription complexes between XPB and XPB/wt-89 cells at the native c-myc promoter. Remarkably, although the mean levels of c-Myc are only modestly elevated in XPB compared to those in XPB/wt-p89 cells, the range of expression and the cell-to-cell variation of c-Myc are markedly increased. Our modeling indicates that the data can be explained if TFIIH integrates inputs from multiple signals, regulating transcription at multiple kinetically equivalent steps between initiation and promoter escape. This helps to suppress the intrinsic noise of transcription and to ensure the steady transcriptional output of c-myc necessary for cellular homeostasis.

* Corresponding author. Mailing address: Gene Regulation Section, Laboratory of Pathology, NCI, CCR, Bldg. 10, Rm. 2N106, Bethesda, MD 20892-1500. Phone: (301) 496-2176. Fax: (301) 594-5227. E-mail: levens{at}helix.nih.gov.

{dagger} A.W. and J.L. are co-first authors.

Molecular and Cellular Biology, January 2005, p. 147-161, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.147-161.2005




This article has been cited by other articles:

  • Pomerantz, M. M., Beckwith, C. A., Regan, M. M., Wyman, S. K., Petrovics, G., Chen, Y., Hawksworth, D. J., Schumacher, F. R., Mucci, L., Penney, K. L., Stampfer, M. J., Chan, J. A., Ardlie, K. G., Fritz, B. R., Parkin, R. K., Lin, D. W., Dyke, M., Herman, P., Lee, S., Oh, W. K., Kantoff, P. W., Tewari, M., McLeod, D. G., Srivastava, S., Freedman, M. L. (2009). Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression. Cancer Res. 69: 5568-5574 [Abstract] [Full Text]  
  • Hsu, K.-W., Hsieh, R.-H., Lee, Y.-H. W., Chao, C.-H., Wu, K.-J., Tseng, M.-J., Yeh, T.-S. (2008). The Activated Notch1 Receptor Cooperates with {alpha}-Enolase and MBP-1 in Modulating c-myc Activity. Mol. Cell. Biol. 28: 4829-4842 [Abstract] [Full Text]  
  • Levens, D. (2008). How the c-myc Promoter Works and Why It Sometimes Does Not. J Natl Cancer Inst Monogr 2008: 41-43 [Abstract] [Full Text]  
  • Liao, W.-R., Hsieh, R.-H., Hsu, K.-W., Wu, M.-Z., Tseng, M.-J., Mai, R.-T., Wu Lee, Y.-H., Yeh, T.-S. (2007). The CBF1-independent Notch1 signal pathway activates human c-myc expression partially via transcription factor YY1. Carcinogenesis 28: 1867-1876 [Abstract] [Full Text]  
  • Park, S. S., Shaffer, A. L., Kim, J. S., duBois, W., Potter, M., Staudt, L. M., Janz, S. (2005). Insertion of Myc into Igh Accelerates Peritoneal Plasmacytomas in Mice. Cancer Res. 65: 7644-7652 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»