Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene.

Ho, I‐Cheng; Vorhees, P; Marín, Nieves; Oakley, Bruce; Tsai, Shih‐Feng; Orkin, Stuart H.; Leiden, Jeffrey M.

doi:10.1002/j.1460-2075.1991.tb08059.x

Cited by 345 publications

(242 citation statements)

References 37 publications

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“…Footprint El encompasses potential binding sites for Ets and Gata family transcription factors. Several Ets family members (Ets-1, Ets-2, and Elf-1) (1, 58) and a Gata family member (Gata-3) are expressed at high levels in T cells (24,27,32). In Jurkat extracts, the region around these two sequences is well protected and includes the presence of a hypersensitive site.…”

Section: Resultsmentioning

confidence: 99%

“…4A). The choices for nucleotide substitutions were based on previous studies in which either factor binding or functional activity of the particular binding site was destroyed (3,23,24,38). These mutant enhancer fragments were subcloned into the luciferase expression vector with the minimal CD4 promoter and transiently transfected into D10 T cells, and the enhancer activity was then compared with activities unmutated enhancer constructs (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Elf-1 binds to a critical element in a second CD4 enhancer.

Wurster¹,

Siu²,

Leiden³

et al. 1994

Mol. Cell. Biol.

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The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells). We have studied the regulation CD4 gene transcription during T-cell development in an attempt to gain an understanding of the molecular mechanisms involved in T-cell development and differentiation. Here we present the identification of a second transcriptional enhancer in the murine CD4 locus 24 kb upstream of the CD4 promoter. This enhancer is active in mature T cells and is especially active in CD4+ helper T cells. A number of nuclear proteins bind to elements in the minimal CD4 enhancer that includes consensus sites for AP-1, Spl, Gata, and Ets transcription factor families. We find that the Ets consensus site is crucial for enhancer activity and that the recently identified Ets factor, Elf-i, which is expressed at high levels in T cells and involved in the regulation of several other T-cell-specific genes, is a dominant protein in T-cell nuclear extracts that binds to this site.T-cell development involves the differentiation of functionally immature pre-T cells into mature, antigen-reactive effector cells (reviewed in reference 61). This process includes selection events in which the maturing T-cell population is depleted of self-reactive clones and enriched for those that can recognize foreign peptides bound by self-major histocompatibility complex (MHC). The development and selection of T-cell precursors occur in the thymus and are characterized by a coordinated expression of tissue-specific genes. Some of these genes encode cell surface molecules that directly promote T-cell differentiation and selection events. Understanding the molecular mechanisms responsible for the expression of these T-cellspecific genes is a window on the process of T-cell development.The CD4 glycoprotein is one of the surface molecules that is important as a receptor in the development and function of T cells (reviewed in references 39 and 46). In mature antigenspecific T cells, CD4 is expressed only on cells that have a T-cell receptor (TCR) specific for antigen associated with class II MHC molecules, while CD8, a cell surface protein functionally similar to CD4, is expressed only on T cells that recognize antigen bound to MHC class I molecules (56). The mutually exclusive expression of CD4 and CD8 on mature T cells also corresponds to T-cell function; CD4 is expressed primarily on helper T cells, while CD8 is expressed on cytotoxic T cells. CD4 participates in antigen recognition by binding to nonpolymorphic regions of class II MHC molecules, while the T-cell antigen receptor recognizes a specific peptide antigen that is bound by the MHC molecule (7). The CD4-MHC interaction serves to increase the avidity of the T cell to the antigenpresenting cell but also induces an intracellular signaling event through the CD4-...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Elf-1 binds to a critical element in a second CD4 enhancer.

Wurster¹,

Siu²,

Leiden³

et al. 1994

Mol. Cell. Biol.

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“…As a result, during development of DP to CD4 SP cells the expression levels of the TCR and GATA3 will increase. It may be possible that GATA3 directly regulates TCRa and b transcription, as binding sites have been identified in these loci [3,36]. As GATA3 expression is not induced in the CD8 cell lineage [5,7], it is clear that different nuclear factors should be responsible for the regulation of the expression levels of CD5 and TCR molecules in the CD8 lineage.…”

Section: Discussionmentioning

confidence: 99%

“…One of the transcription factors indispensable for CD4 lineage development is the zinc-finger transcriptional regulator GATA3, which was originally identified as a protein that binds to the TCRa gene enhancer [3]. GATA3 is indispensable for early T cell lineage development and also plays a crucial role in the differentiation of mature Th2 effector cells by regulating transcription and chromatin configuration of the IL-4, IL-5 and IL-13 Th2 cytokine genes (reviewed in [4]).…”

Section: Introductionmentioning

confidence: 99%

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

et al. 2007

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The transcription factor GATA3 is essential at multiple stages of T cell development, including the earliest double-negative stages, b-selection and CD4 single-positive thymocytes. Here, we show that in CD2-GATA3 transgenic mice, with enforced GATA3 expression driven by the CD2 promoter, thymocytes have reduced levels of CD5, which is a negative regulator of TCR signaling participating in TCR repertoire fine-tuning. Reduction of CD5 expression was most prominent in CD4 + CD8 + double-positive (DP) cells and was associated with increased levels of the transcription factor E2A. Conversely, GATA3-deficient DP thymocytes showed consistently higher CD5 levels and defective TCR up-regulation during their development towards the CD4 lo CD8 lo subpopulation. CD2-GATA3 transgenic mice carrying the MHC class II-restricted TCR DO11.10 also manifested decreased CD5 levels. As in these TCR-transgenic mice reduced CD5 expression cannot result from an effect of GATA3 on repertoire selection, we conclude that enforced GATA3 interferes with the developmentally regulated increase of CD5 levels. Enforced GATA3 expression in DO11.10 transgenic mice was also accompanied by enhanced TCR expression during CD4 positive selection. Because GATA3 is induced by TCR signaling in DP thymocytes, our findings indicate that GATA3 establishes a positive feedback loop that increases TCR surface expression in developing CD4 lineage cells.

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“…Random site selection has suggested that additional nonconsensus sequences can bind GATA proteins with high affinity (32,42). Two of the GATA transcription factors (GATA-1 and GATA-3) are expressed in a tissuerestricted fashion and have been shown previously to regulate lineage-specific gene expression in erythroid cells and T lymphocytes, respectively (24,29,33,72,78). Moreover, homozygous disruption of the GATA-1 gene in mice results in a specific block in erythroid development (56,68).…”

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confidence: 99%

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

Ip¹,

Wilson²,

Heikinheimo³

et al. 1994

Mol. Cell. Biol.

171

104

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The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineagerestricted zinc finger transcription factor GATA-4. This (7, 10,27,35,48,65,81). Therefore, an understanding of muscle cell development must at some level be based upon elucidating the molecular mechanisms that control lineage-specific gene expression during myogenesis.The recent identification and characterization of the basic helix-loop-helix myogenic transcription factors, including MyoD, myogenin, Myf-5, and MRF-4/herculin/Myf-6, as well as the MEF-2 family of transcription factors has added significantly to our understanding of skeletal myogenesis (8, 9,12,15,18,40,41,43,58,59,76,80). These factors bind to and regulate the expression of many skeletal muscle-specific genes (47,48,64,70). In contrast, relatively little is currently understood about the molecular mechanisms that control cardiac muscle-specific gene expression during mammalian development. Despite the fact that overlapping sets of genes are expressed in the heart and skeletal muscle, several lines of evidence suggest that distinct transcriptional programs may regulate these processes. For example, basic helix-loop-helix myogenic transcription factors are not expressed in developing heart or precardiac mesoderm (49,63,64), and mice contain-* Corresponding author. Mailing address:

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Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene.

Cited by 345 publications

References 37 publications

Elf-1 binds to a critical element in a second CD4 enhancer.

Elf-1 binds to a critical element in a second CD4 enhancer.

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

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