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* Division of Pediatric Hematology-Oncology, Children’s Hospital,
Department of Pediatric Oncology,
Department of Medical Oncology, Dana-Farber Cancer Institute,
Harvard Medical School, and
¶ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115
GATA-3, the only T cell-specific member of the GATA family of transcription factors, is essential for the intrathymic development of CD4+ T cells and for the differentiation of Th2 cells. However, whether distinct biochemical features, unique to GATA-3 compared with other GATA family members, are required to drive T cell transcriptional programs or whether the T cell-specific functions of GATA-3 can simply be ascribed to its expression pattern is unclear. Nor do we understand the protein structural requirements for each individual function of GATA-3. In this study, we report that a heterologous GATA factor, GATA-4, was competent in supporting the development of CD4+ T cells but could not fully compensate for GATA-3 in regulating the expression of Th cytokines. Specifically, GATA-3 was more potent than GATA-4 in driving the production of IL-13 due to a mechanism independent of DNA binding or chromatin remodeling of the IL-13 locus. The difference was mapped to a partially conserved region C-terminal to the second zinc finger. Converting a single proline residue located in this region of GATA-4 to its counterpart, a methionine of GATA-3, was sufficient to enhance the IL-13-promoting function of GATA-4 but had no effect on other cytokines. Taken together, our data demonstrate that the unique function of GATA-3 is conferred by both its cell type-specific expression and distinct protein structure.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant R01 AI054451 (to I.-C.H.) and a K08 AI050601 Award (to S.-Y.P.) from the National Institutes of Health and a Charles H. Hood Foundation Child Health Research Grant (to S.-Y.P.).
2 Current address: Chonnam National University, Gwangju, Republic of Korea.
3 Current addresses: Biomedical Sciences Program, University of California, San Francisco, CA 94143.
4 Address correspondence and reprint requests to Dr. I-Cheng Ho, Smith Building, One Jimmy Fund Way, Boston, MA 02115. E-mail address: iho{at}partners.org
5 Abbreviations used in this paper: SP, single positive; FF, floxed.
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