Distinct structural requirements of GATA-3 for the regulation of thymocyte and Th2 cell differentiation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sung-Yun PaiI-Cheng Ho

Abstract

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 c...Continue Reading

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Citations

Sep 17, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Catherine A NewtonThomas W Klein
Jan 6, 2017·EMBO Molecular Medicine·Mona Malek MohammadiJoerg Heineke
Dec 24, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Sheikh RayeesGurdarshan Singh

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