GATA-3 - not just for Th2 cells anymore

Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cellular & molecular immunology (Impact Factor: 4.11). 03/2007; 4(1):15-29.
Source: PubMed


GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system.

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Available from: Sung-Yun Pai, Oct 06, 2015
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    • "However, the expression and function of GATA and Sp1 factors in helper T lymphocytes (Th cells, CD4+ lymphocytes) is still poorly understood. GATA3 is considered to be the only GATA member that is expressed in CD4+ lymphocytes (reviewed in [12]). The transcriptional activity of Sp1 has been described in proliferating T lymphocytes and is presumably involved in cell cycle regulation [19]. "
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    ABSTRACT: We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4(+) lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells' function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4(+) lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4(+) cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4(+) lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4(+) lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells' surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4(+) lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4(+) lymphocytes.
    PLoS ONE 04/2013; 8(4):e60326. DOI:10.1371/journal.pone.0060326 · 3.23 Impact Factor
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    • "This phenotype is representative of the basal subtype of tumors, which are negative for ER and HER2 expression. In breast, GATA-3 plays an important role in mammary gland development and differentiation (Bossard and Zaret 1998; Ho and Pai 2007). Moreover, the inactivation of GATA-3 in mice results in contracted mammary epithelial structure, severely impaired lactogenesis, and disrupted differentiation of luminal progenitor cells into ductal and alveolar cells (Asselin-Labat et al. 2007). "
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    ABSTRACT: Estrogen receptor (ER) is a hormone-regulated transcription factor that controls cell division and differentiation in the ovary, breast, and uterus. The expression of ER is a common feature of the majority of breast cancers, which is used as a therapeutic target. Recent genetic studies have shown that ER binding occurs in regions distant to the promoters of estrogen target genes. These studies have also demonstrated that ER binding is accompanied with the binding of other transcription factors, which regulate the function of ER and response to anti-estrogen therapies. In this review, we explain how these factors influence the interaction of ER to chromatin and their cooperation for ER transcriptional activity. Moreover, we describe how the expression of these factors dictates the response to anti-estrogen therapies. Finally, we discuss how cytoplasmatic signaling pathways may modulate the function of ER and its cooperating transcription factors.
    Chromosoma 11/2012; 122(1-2). DOI:10.1007/s00412-012-0392-7 · 4.60 Impact Factor
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    • "GATA-3 plays at least three roles in T cell development: during initial specification, during TCRαβ-dependent positive selection, and in mature T cells where it establishes the Th2 effector program. In the Th2 context the addition of GATA-3 clearly promotes Th2 fate just as loss of GATA-3 inhibits it [23] [24]. In TCRαβ-mediated positive selection of CD4 + lineage thymocytes its effects can be more complicated, but again the gain of function of GATA-3 promotes the CD4 + fate relative to other options [25] [26] [27]. "
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    ABSTRACT: The T-cell development program is specifically triggered by Notch-Delta signaling, but most transcription factors needed to establish T-cell lineage identity also have crossover roles in other hematopoietic lineages. This factor sharing complicates full definition of the core gene regulatory circuits required for T-cell specification. But new advances illuminate the roles of three of the most T-cell specific transcription factors. Commitment to the T-cell lineage is now shown to depend on Bcl11b, while initiation of the T-cell differentiation program begins earlier with the induction of TCF-1 (Tcf7 gene product) and GATA-3. Several reports now reveal how TCF-1 and GATA-3 are mobilized in early T cells and the pathways for their T-lineage specific effects.
    Current opinion in immunology 01/2012; 24(2):132-8. DOI:10.1016/j.coi.2011.12.012 · 7.48 Impact Factor
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