Article

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: 4.19). 03/2007; 4(1):15-29.
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Sung-Yun Pai, Aug 27, 2015
1 Follower
 · 
148 Views
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 3.26 Impact Factor
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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 · 7.87 Impact Factor
  • Source
    • "The GATA protein family can be divided by body distribution. GATA1–3 are primarily expressed in hematopoietic cells while GATA4–6 are expressed in endoderm-derived tissues (Ho and Pai, 2007). GATA3, a protein essential for regulating Th2 development and function, is expressed during human kidney embryogenesis (Labastie et al., 1995) with GATA3 haploinsufficiency responsible for hypoparathyroidism, sensorineural deafness and renal anomalies (HDR) syndrome in humans (Van Esch et al., 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Loss of transforming growth factor-beta receptor III (TbetaRIII) correlates with loss of transforming growth factor-beta (TGF-beta) responsiveness and suggests a role for dysregulated TGF-beta signaling in clear cell renal cell carcinoma (ccRCC) progression and metastasis. Here we identify that for all stages of ccRCC TbetaRIII expression is downregulated in patient-matched tissue samples and cell lines. We find that this loss of expression is not due to methylation of the gene and we define GATA3 as the first transcriptional factor to positively regulate TbetaRIII expression in human cells. We localize GATA3's binding to a 10-bp region of the TbetaRIII proximal promoter. We demonstrate that GATA3 mRNA is downregulated in all stages, of ccRCC, mechanistically show that GATA3 is methylated in ccRCC patient tumor tissues as well as cell lines, and that inhibiting GATA3 expression in normal renal epithelial cells downregulates TbetaRIII mRNA and protein expression. These data support a sequential model whereby loss of GATA3 expression through epigenetic silencing decreases TbetaRIII expression during ccRCC progression.
    Oncogene 03/2010; 29(20):2905-15. DOI:10.1038/onc.2010.64 · 8.56 Impact Factor
Show more