| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Hanson Center for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia
The human IL-3 gene is expressed by activated T cells, mast cells, and eosinophils. We previously identified an enhancer 14 kb upstream of the IL-3 gene, but this element only functioned in a subset of T cells and not in mast cells. To identify additional mechanisms governing IL-3 gene expression, we mapped DNase I hypersensitive (DH) sites and evolutionarily conserved DNA sequences in the IL-3 locus. The most conserved sequence lies 4.5 kb upstream of the IL-3 gene and it encompassed an inducible cyclosporin A-sensitive DH site. A 245-bp fragment spanning this DH site functioned as a cyclosporin A-sensitive enhancer, and was induced by calcium and kinase signaling pathways in both T cells and mast cells via an array of three NFAT sites. The enhancer also encompassed AML1, AP-1, and Sp1 binding sites that potentially mediate function in both T and myeloid lineage cells, but these sites were not required for in vitro enhancer function in T cells. In stably transfected T cells, the -4.5-kb enhancer cooperated with the -14-kb enhancer to activate the IL-3 promoter. Hence, the IL-3 gene is regulated by two enhancers that have distinct but overlapping tissue specificities. We also identified a prominent constitutive DH site at -4.1 kb in T cells, mast cells, and CD34+ myeloid cells. This element lacked in vitro enhancer function, but may have a developmental role because it appears to be the first DH site to exist upstream of the IL-3 gene during hemopoietic development before IL-3 expression.
This article has been cited by other articles:
|
|
 |
|
  N. Soto-Nieves, I. Puga, B. T. Abe, S. Bandyopadhyay, I. Baine, A. Rao, and F. Macian Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance J. Exp. Med., April 13, 2009; 206(4): 867 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Bowers, F. Mirabella, F. J. Calero-Nieto, S. Valeaux, S. Hadjur, E. W. Baxter, M. Merkenschlager, and P. N. Cockerill 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., April 1, 2009; 29(7): 1682 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Sly, J. Kalesnikoff, V. Lam, D. Wong, C. Song, S. Omeis, K. Chan, C. W. K. Lee, R. P. Siraganian, J. Rivera, et al. IgE-Induced Mast Cell Survival Requires the Prolonged Generation of Reactive Oxygen Species J. Immunol., September 15, 2008; 181(6): 3850 - 3860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Mellstrom, M. Savignac, R. Gomez-Villafuertes, and J. R. Naranjo Ca2+-Operated Transcriptional Networks: Molecular Mechanisms and In Vivo Models Physiol Rev, April 1, 2008; 88(2): 421 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Y.-N. Lee, J. Tuckerman, H. Nechushtan, G. Schutz, E. Razin, and P. Angel c-Fos as a Regulator of Degranulation and Cytokine Production in Fc{epsilon}RI-Activated Mast Cells J. Immunol., August 15, 2004; 173(4): 2571 - 2577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Lee, H. Y. Chung, L. A. Ehrlich, D. F. Jelinek, N. S. Callander, G. D. Roodman, and S. J. Choi IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells Blood, March 15, 2004; 103(6): 2308 - 2315. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
