| First Author | Pai SY | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 2 | Pages | 1050-9 |
| PubMed ID | 18178845 | Mgi Jnum | J:130983 |
| Mgi Id | MGI:3772623 | Doi | 10.4049/jimmunol.180.2.1050 |
| Citation | Pai SY, et al. (2008) Distinct structural requirements of GATA-3 for the regulation of thymocyte and Th2 cell differentiation. J Immunol 180(2):1050-9 |
| abstractText | 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. |
