Gata3 Gene

Acronym for "glutamyl aminotransferase subunit A". GATA3 refers to a gene located on chromosome 10p15. The encoded protein GATA3 , acts as a broad transcription factor that switches other genes on and off.

The GATA3 protein and other members of the GATA gene family, play a key role in the normal development and regeneration of cells. This is also true for the hematopoietic system.

GATA3 only occurs within the cells. The encoded GATA3 protein is considered the key transcription factor for T-cell differentiation along with the transcription factors TBX21 (T-bet, T-box expressed in T-cells) and HLX1 (H 2.0-like homeobox).

While the combination of T-bet and HLX1 controls the Th1 immune response, GATA3 is responsible for the development and maintenance of Th2 response.

Characteristic for the Th2 cells (see below T-helper lymphocyte) is the interaction with B cells. This interaction is essential for example to eliminate an extracellular pathogen.

GATA regulates the release of the typical Th2 cytokines interleukin-4, interleukin-5, interleukin-6, interleukin-10, interleukin-13 and TGF-beta. Expression data on GATA3 show that GATA3 is strongly expressed in Th2 cells but poorly expressed in Th1 cells.

The Th2 differentiation process is mainly controlled by the cytokines IL-4 and IL-13. The binding of these cytokines to their receptors on naïve T cells leads via the Janus tyrosine kinases (JAK) 1 and 3 to the activation of the transcription factor STAT6 (signal transducer and activator of transcription protein 6). STAT6 then interacts directly with GATA3 to initiate Th2 differentiation.

In the mouse model, blocking GATA3 led to the inhibition of Th2 cytokine production in already differentiated Th2 cells. Even in the absence of the Th1-specific cytokines INFgamma and IL-12 the Th1 response is initiated. For TBX21, also for GATA3, it could be shown that both transcription factors have the ability to competitively suppress the cytokine pattern of the respective other T-subpopulation and thus promote the development process of their own differentiation.

GATA3 is expressed and upregulated by secary cells, which leads to Th2 reactivity, suppression of the Th-1 response and a general Th1/Th2 imbalance. It is remarkable that the "normal" Th2 cell lacks the ability to recruit into the skin. Thus, other factors will also be responsible for this.

GATA3 also has the property of "autoactivation", i.e. it is able to stimulate its own expression independently of STAT6 and thus stabilize Th2 cell differentiation.

1. Davis DG et al (2016) GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas. Hum Pathol 47: 26-31.
2. Hosokawa H et al (2016) Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells. Nat Commun 7:11289.
3. Mertens RB et al (2015) GATA3 expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms. At J Dermatopathol 37: 885-891.
4. Nicolay JP et al (2016) Sézary syndrome: from unresolved questions to new therapeutic approaches. JDDG 14: 256-265
5. Takaku M et al (2015) GATA3 in Breast Cancer: Tumor Suppressor or Oncogene? Gene Expr 16:163-168.