An intron GATA‐binding site regulates chromatin accessibility and is essential for IL‐4 gene expression in mast cells
Open Access
- 22 March 2005
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 35 (4), 1267-1274
- https://doi.org/10.1002/eji.200425619
Abstract
Several GATA-binding sites have been identified in regions both distal to and within the murine IL-4 gene locus, yet their relative role in IL-4 expression is unknown. Chromatin immunoprecipitation assays were used to demonstrate that GATA-1 and GATA-2 are associated with a regulatory element within the second intron of the IL-4 gene in murine mast cells in vivo. Furthermore, although expression from a stably integrated wild-type IL-4 minigene parallels endogenous IL-4 gene expression, mutation of the GATA-binding element, but not an SP-1-binding site, virtually abolishes transcription in mast cells, an observation that correlates with the local loss of H3 and H4 histone acetylation in the intron. Treatment with the chromatin remodeling agents 5 azacytidine and trichostatin A can restore this defect in transcription. These results define an essential site of GATA influence on IL-4 expression in mast cells and directly support the idea that GATA factors have a profound impact on locus accessibility.Keywords
This publication has 36 references indexed in Scilit:
- Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cellsNature Immunology, 2003
- A 3′ Enhancer in the IL-4 Gene Regulates Cytokine Production by Th2 Cells and Mast CellsImmunity, 2002
- Proteolytic Processing of Stat6 Signaling in Mast Cells as a Negative Regulatory MechanismThe Journal of Experimental Medicine, 2002
- The language of covalent histone modificationsNature, 2000
- Induction of Germline Transcription in the TCRγ Locus by Stat5: Implications for Accessibility Control by the IL-7 ReceptorImmunity, 1999
- ETS Protein–Dependent Accessibility Changes at the Immunoglobulin μ Heavy Chain EnhancerImmunity, 1999
- GATA-3 Significantly Downregulates IFN-γ Production from Developing Th1 Cells in Addition to Inducing IL-4 and IL-5 LevelsClinical Immunology, 1999
- Physical and functional interactions between the transcription factor PU.1 and the coactivator CBPOncogene, 1999
- The Proto-Oncogene c-maf Is Responsible for Tissue-Specific Expression of Interleukin-4Cell, 1996
- Stat6 Is Required for Mediating Responses to IL-4 and for the Development of Th2 CellsImmunity, 1996