| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Human Immunology, Hanson Centre For Cancer Research, Institute for Medical and Veterinary Science, Adelaide, Australia
The complex nature of most promoters and enhancers makes it difficult to identify key determinants of tissue-specific gene expression. Furthermore, most tissue-specific genes are regulated by transcription factors that have expression profiles more widespread than the genes they control. NFAT is an example of a widely expressed transcription factor that contributes to several distinct patterns of cytokine gene expression within the immune system and where its role in directing specificity remains undefined. To investigate distinct combinatorial mechanisms employed by NFAT to regulate tissue-specific transcription, we examined a composite NFAT/AP-1 element from the widely active GM-CSF enhancer and a composite NFAT/Oct element from the T cell-specific IL-3 enhancer. The NFAT/AP-1 element was active in the numerous cell types that express NFAT, but NFAT/Oct enhancer activity was T cell specific even though Oct-1 is ubiquitous. Conversion of the single Oct site in the IL-3 enhancer to an AP-1 enabled activation outside of the T cell lineage. By reconstituting the activities of both the IL-3 enhancer and its NFAT/Oct element in a variety of cell types, we demonstrated that their T cell-specific activation required the lymphoid cofactors NIP45 and OCA-B in addition to NFAT and Oct family proteins. Furthermore, the Oct family protein Brn-2, which cannot recruit OCA-B, repressed NFAT/Oct enhancer activity. Significantly, the two patterns of combinatorial regulation identified in this study mirror the cell-type specificities of the cytokine genes that they govern. We have thus established that simple composite transcription factor binding sites can indeed establish highly specific patterns of gene expression.
This article has been cited by other articles:
|
|
 |
|
  A. G. Bert, B. V. Johnson, E. W. Baxter, and P. N. Cockerill 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., April 15, 2007; 27(8): 2870 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. V. Johnson, A. G. Bert, G. R. Ryan, A. Condina, and P. N. Cockerill Granulocyte-Macrophage Colony-Stimulating Factor Enhancer Activation Requires Cooperation between NFAT and AP-1 Elements and Is Associated with Extensive Nucleosome Reorganization Mol. Cell. Biol., September 15, 2004; 24(18): 7914 - 7930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Goodall, S. Martinozzi, T. J. Dexter, D. Champeval, S. Carreira, L. Larue, and C. R. Goding Brn-2 Expression Controls Melanoma Proliferation and Is Directly Regulated by {beta}-Catenin Mol. Cell. Biol., April 1, 2004; 24(7): 2915 - 2922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Goodall, C. Wellbrock, T. J. Dexter, K. Roberts, R. Marais, and C. R. Goding The Brn-2 Transcription Factor Links Activated BRAF to Melanoma Proliferation Mol. Cell. Biol., April 1, 2004; 24(7): 2923 - 2931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Hogan, L. Chen, J. Nardone, and A. Rao Transcriptional regulation by calcium, calcineurin, and NFAT Genes & Dev., September 15, 2003; 17(18): 2205 - 2232. [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. C. Yang and C.-W. Chow Transcription Cooperation by NFAT{middle dot}C/EBP Composite Enhancer Complex J. Biol. Chem., April 25, 2003; 278(18): 15874 - 15885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Bower, R. W. Zeller, W. Wachsman, T. Martinez, and K. L. McGuire Correlation of Transcriptional Repression by p21SNFT with Changes in DNA{middle dot}NF-AT Complex Interactions J. Biol. Chem., September 13, 2002; 277(38): 34967 - 34977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hawwari, J. Burrows, M. A. Vadas, and P. N. Cockerill The Human IL-3 Locus Is Regulated Cooperatively by Two NFAT-Dependent Enhancers That Have Distinct Tissue-Specific Activities J. Immunol., August 15, 2002; 169(4): 1876 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhou, R. Q. Cron, B. Wu, A. Genin, Z. Wang, S. Liu, P. Robson, and H. S. Baldwin Regulation of the Murine Nfatc1 Gene by NFATc2 J. Biol. Chem., March 15, 2002; 277(12): 10704 - 10711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lefevre, J. Kontaraki, and C. Bonifer Identification of factors mediating the developmental regulation of the early acting -3.9 kb chicken lysozyme enhancer element Nucleic Acids Res., November 15, 2001; 29(22): 4551 - 4560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Houlard, R. Arudchandran, F. Regnier-Ricard, A. Germani, S. Gisselbrecht, U. Blank, J. Rivera, and N. Varin-Blank Vav1 Is a Component of Transcriptionally Active Complexes J. Exp. Med., May 6, 2002; 195(9): 1115 - 1127. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
