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 Johnson, B. V.
Right arrow Articles by Cockerill, P. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johnson, B. V.
Right arrow Articles by Cockerill, P. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2004, p. 7914-7930, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.7914-7930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Granulocyte-Macrophage Colony-Stimulating Factor Enhancer Activation Requires Cooperation between NFAT and AP-1 Elements and Is Associated with Extensive Nucleosome Reorganization

Brett V. Johnson,1 Andrew G. Bert,2 Gregory R. Ryan,2 Antony Condina,2 and Peter N. Cockerill1*

Molecular Medicine Unit, Department of Medicine, St. James’s University Hospital, University of Leeds, Leeds, England,1 Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia2

Received 20 December 2003/ Returned for modification 20 January 2004/ Accepted 22 June 2004

The human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is activated by an NFAT-dependent enhancer forming an inducible DNase I hypersensitive (DH) site. The enhancer core comprising the DH site contains the GM330 and GM420 elements that bind NFAT and AP-1 cooperatively. Here we demonstrate that both elements are essential for enhancer activity and that Sp1 and AML1 sites in the enhancer become occupied in vivo only after activation. Chromatin structure analysis revealed that the GM-CSF enhancer core elements are divided between two adjacent nucleosomes that become destabilized and highly accessible after activation. Inducible chromatin reorganization was not restricted to the enhancer core but extended across a 3-kb domain of mobilized nucleosomes, within which the nucleosome repeat length was compressed from approximately 185 to 150 bp. The GM420 element is a high-affinity site that binds NFAT independently of AP-1 but depends on the linked AP-1 site for enhancer function. Nevertheless, just the NFAT motif from the GM420 element was sufficient to form a DH site within chromatin even in the absence of the AP-1 site. Hence, NFAT has the potential to cooperate with other transcription factors by promoting chromatin remodelling and increasing accessibility at inducible regulatory elements.

* Corresponding author. Mailing address: Molecular Medicine Unit, Department of Medicine, University of Leeds, Clinical Sciences Building, St. James's University Hospital, Leeds LS9 7TF, England. Phone: 44 113 2065642. Fax: 44 113 2444475. E-mail: p.n.cockerill{at}leeds.ac.uk.

Molecular and Cellular Biology, September 2004, p. 7914-7930, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.7914-7930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vardarova, K., Scharf, S., Lang, F., Schmeck, B., Opitz, B., Eitel, J., Hocke, A. C., Slevogt, H., Flieger, A., Hippenstiel, S., Suttorp, N., N'Guessan, P. D. (2009). PKC{alpha} and PKC{epsilon} differentially regulate Legionella pneumophila-induced GM-CSF. Eur Respir J 34: 1171-1179 [Abstract] [Full Text]  
  • Ndlovu, M. N., Van Lint, C., Van Wesemael, K., Callebert, P., Chalbos, D., Haegeman, G., Vanden Berghe, W. (2009). Hyperactivated NF-{kappa}B and AP-1 Transcription Factors Promote Highly Accessible Chromatin and Constitutive Transcription across the Interleukin-6 Gene Promoter in Metastatic Breast Cancer Cells. Mol. Cell. Biol. 29: 5488-5504 [Abstract] [Full Text]  
  • Soto-Nieves, N., Puga, I., Abe, B. T., Bandyopadhyay, S., Baine, I., Rao, A., Macian, F. (2009). Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance. JEM 206: 867-876 [Abstract] [Full Text]  
  • Bowers, S. R., Mirabella, F., Calero-Nieto, F. J., Valeaux, S., Hadjur, S., Baxter, E. W., Merkenschlager, M., Cockerill, P. N. (2009). A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes. Mol. Cell. Biol. 29: 1682-1693 [Abstract] [Full Text]  
  • Falvo, J. V., Lin, C. H., Tsytsykova, A. V., Hwang, P. K., Thanos, D., Goldfeld, A. E., Maniatis, T. (2008). A dimer-specific function of the transcription factor NFATp. Proc. Natl. Acad. Sci. USA 105: 19637-19642 [Abstract] [Full Text]  
  • Karpurapu, M., Wang, D., Singh, N. K., Li, Q., Rao, G. N. (2008). NFATc1 Targets Cyclin A in the Regulation of Vascular Smooth Muscle Cell Multiplication during Restenosis. J. Biol. Chem. 283: 26577-26590 [Abstract] [Full Text]  
  • Brettingham-Moore, K. H., Sprod, O. R., Chen, X., Oakford, P., Shannon, M. F., Holloway, A. F. (2008). Determinants of a transcriptionally competent environment at the GM-CSF promoter. Nucleic Acids Res 36: 2639-2653 [Abstract] [Full Text]  
  • Cockerill, P. N. (2008). NFAT Is Well Placed to Direct Both Enhancer Looping and Domain-Wide Models of Enhancer Function. Sci Signal 1: pe15-pe15 [Abstract] [Full Text]  
  • Kaminuma, O., Kitamura, F., Kitamura, N., Hiroi, T., Miyoshi, H., Miyawaki, A., Miyatake, S. (2008). Differential Contribution of NFATc2 and NFATc1 to TNF-{alpha} Gene Expression in T Cells. J. Immunol. 180: 319-326 [Abstract] [Full Text]  
  • Helms, W. S., Jeffrey, J. L., Holmes, D. A., Townsend, M. B., Clipstone, N. A., Su, L. (2007). Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T cells. J. Leukoc. Biol. 82: 361-369 [Abstract] [Full Text]  
  • Bert, A. G., Johnson, B. V., Baxter, E. W., Cockerill, P. N. (2007). A Modular Enhancer Is Differentially Regulated by GATA and NFAT Elements That Direct Different Tissue-Specific Patterns of Nucleosome Positioning and Inducible Chromatin Remodeling. Mol. Cell. Biol. 27: 2870-2885 [Abstract] [Full Text]  
  • Hidalgo-Estevez, A. M., Gonzalez, E., Punzon, C., Fresno, M. (2006). Human immunodeficiency virus type 1 Tat increases cooperation between AP-1 and NFAT transcription factors in T cells. J. Gen. Virol. 87: 1603-1612 [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»