Regulation of GATA-3 Expression during CD4 Lineage Differentiation

@article{Gimferrer2011RegulationOG,
  title={Regulation of GATA-3 Expression during CD4 Lineage Differentiation},
  author={Idoia Gimferrer and Taishan Hu and Amie Simmons and Chi Wang and Abdallah Souabni and Meinrad Busslinger and Timothy P. Bender and Gabriela Hernández-Hoyos and Jos{\'e} Alberola-Ila},
  journal={The Journal of Immunology},
  year={2011},
  volume={186},
  pages={3892 - 3898}
}
GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the… 
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Methods Citations
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RNA interference and conditional deletion are used to reduce GATA-3 protein acutely at specific points during T cell differentiation in vitro to mediate two distinct roles played by Gata-3 in lineage commitment, as revealed by removing wild-type or GATA–deflcient early T lineage cells from environmental Notch signals.
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TOX Is Required for Development of the CD4 T Cell Lineage Gene Program
TLDR
Investigation of the requirement for nuclear protein TOX in CD4+ T cell development sought to investigate whether the requirement was solely due to a role in ThPOK induction, and in apparent support of this proposition, ThPok upregulation and CD8 lineage repression were compromised in the absence of TOX.
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TLDR
Pharmacological inhibition validates the requirement of calcineurin- NFAT for CD4, but not CD8, lineage development, providing insight into the CD4/CD8 commitment mechanism.
Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3
TLDR
It is shown that maintenance of Gata3 protein levels by Myb and Notch signaling is linked to the ability to retain T-cell identity in response to PU.1, and two branches of this network are described.
Analysis of a transcriptional network involving PU.1, Notch, and Gata3 in the lymphomyeloid lineage decision during early T-cell development
TLDR
This work characterized an early T-cell cell line, Scid.adh.2c2, as a good model system for studying the myeloid vs. lymphoid developmental choice dependent on PU.1 and Notch signaling, and identified mechanisms mediating PU.3-mediated inhibition and E-protein inhibition that leads to the inhibition of Notch target genes.
Transcriptional regulation of early T‐cell development in the thymus
TLDR
This review summarizes recent advances in knowledge on thymic T‐cell development from newly arrived multipotent T‐ cell progenitors to fully committed T-cell precursors, from the transcriptional regulation perspective.
Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.
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References

SHOWING 1-10 OF 46 REFERENCES
GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation.
Critical roles for transcription factor GATA-3 in thymocyte development.
Expression of GATA-3 During Lymphocyte Differentiation and Mouse Embryogenesis
TLDR
The GATA family of C4 zinc-finger transcription factors has been implicated in tissuespecific gene regulation in birds and mammals and its expression pattern is documented, providing new clues about the potential role of GATA-3 during mouse development and will aid the interpretation of currently ongoing gene knockout experiments.
Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells
TLDR
Gata3 disruption blocked differentiation into theCD4+ T cell lineage before commitment to the CD4+ lineage and in some contexts permitted the 'redirection' of major histocompatibility complex class II–restricted thymocytes into the CD8+ lineage.
Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.
Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection
TLDR
The identification of the Egr family in this context represents the first report of a link between the two known signaling pathways involved in positive selection and downstream transcriptional regulators.
Transcription factor GATA-3 is required for development of the T-cell lineage
TLDR
The results show that GATA-3−/− ES cells can contribute to the development of the mature ery-throid, myelomonocytic and B-cell lineages, but fail to give rise to thymocytes or mature peripheral T cells, suggesting that Gata-3 is an essential and specific regulator of early thymocyte development.
CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus.
The role of ThPOK in control of CD4/CD8 lineage commitment.
TLDR
This review deals with three formerly discrete topics that are gradually becoming interconnected: the role of TCR signaling in lineage commitment, the regulation of expression of the CD4 and CD8 genes, and transcriptional regulation of lineage commitment.
Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus
TLDR
It is found that the T cell development from FL, but not FT, progenitors in the FT organ culture system is severely inhibited by the addition of antisense oligonucleotides for either TCF-1 or GATA-3.
...
...