A T-cell specific TCR delta DNA binding protein is a member of the human GATA family.

Joulin, Virginie; Bories, Dominique; Eléouët, Jean François; Labastie, Marie-Claude; Chrétien, Stany; Mattéi, Marie Geneviève; Roméo, Paul‐Henri

doi:10.1002/j.1460-2075.1991.tb07706.x

Cited by 166 publications

(116 citation statements)

References 35 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%

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%

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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“…9), we conclude that GATA3 probably regulates allelic exclusion through novel pathways, with one likely possibility being that a presently undefined transcriptional target of GATA3 directly promotes Tcrb rearrangement. GATA3 binds to the (A/T)GATAA sequence (29,57,58) in chromatin, and while not ubiquitously expressed, GATA3 has been shown to function as either a transcriptional activator or a repressor in many different tissues and cell types (29,30,(59)(60)(61)(62)(63). A second viable hypothesis is that GATA3 directly controls the accessibility or nuclear localization of the Tcrb loci in chromatin (64), and it is this feature of the nuclear architecture that is regulated in the GATA3 pathway.…”

Section: Discussionmentioning

confidence: 99%

GATA3 Abundance Is a Critical Determinant of T Cell Receptor β Allelic Exclusion

Sekiguchi

Panwar

et al. 2017

Molecular and Cellular Biology

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Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild-type mammals, approximately 60% of cells have recombined the DNA of one T cell receptor ␤ (TCR␤) V-to-DJ-joined allele in a functional configuration, while the second allele has recombined only the DJ sequences; the other 40% of cells have recombined the V to the DJ segments on both alleles, with only one of the two alleles predicting a functional TCR␤ protein. Here we report that the transgenic overexpression of GATA3 leads predominantly to biallelic TCR␤ gene (Tcrb) recombination. We also found that wild-type immature thymocytes can be separated into distinct populations based on intracellular GATA3 expression and that GATA3 LO cells had almost exclusively recombined only one Tcrb locus (that predicted a functional receptor sequence), while GATA3 HI cells had uniformly recombined both Tcrb alleles (one predicting a functional and the other predicting a nonfunctional rearrangement). These data show that GATA3 abundance regulates the recombination propensity at the Tcrb locus and provide new mechanistic insight into the historic immunological conundrum for how Tcrb allelic exclusion is mediated.KEYWORDS allelic exclusion, T cell receptor beta locus, GATA3, monoallelic-tobiallelic switch O ne enduring mystery in cellular immunology regards the underlying mechanisms that control antigen receptor allelic exclusion (1, 2), the process whereby B or T lymphocytes are programmed to express only one functional allele for each chain of their respective antigen receptors (B cell receptor [BCR] or T cell receptor [TCR]), thus avoiding the coexistence of multiple antigen specificities in a single immune cell. Lymphocytes acquire the diversity of antigen recognition (3) as well as a unique monospecificity for particular antigens (4) during development in the bone marrow (B cells) or the thymus (T cells).T lymphocyte development is generally characterized by division into multiple stages based on developmental timing and the location and expression of specific cell surface markers (5). T cell development begins when multipotential hematopoietic progenitor cells in the bone marrow migrate through the bloodstream to the thymus, where early T lineage progenitors (ETPs) are generated and later specified to become T cells (6-10). ETPs differentiate into double-negative (DN) cells (DN2 to DN4 stages) that express neither the CD4 nor the CD8 coreceptor, then into double-positive (DP)

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“…GATA3 is located at chromosome 10p15 [2]. GATA 1, 2 and 3 are critically involved in myeloerythropoiesis whereas GATA 4, 5 and 6 are implicated in cardiac and intestinal development [3].…”

Section: Introductionmentioning

confidence: 99%