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 also applies to the hematopoietic system.

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

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

A characteristic feature of Th2 cells (see T helper lymphocyte below) is their interaction with B cells. This interaction is essential in order to eliminate an extracellular pathogen, for example.

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 hardly 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 to the activation of the transcription factor STAT6 (signal transducer and activator of transcription protein 6) via Janus tyrosine kinases (JAK) 1 and 3. STAT6 then interacts directly with GATA3 to initiate Th2 differentiation.

In the mouse model, blocking GATA3 led to the abolition 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 then initiated. It has been shown for TBX21 and GATA3 that both transcription factors have the ability to competitively suppress the cytokine pattern of the other T subpopulation and thus promote the development process of their own differentiation.

GATA3 is expressed and upregulated by Sezary cells, leading to Th2 reactivity, suppression of the Th-1 response and a general Th1/Th2 imbalance. It is noteworthy that the "normal" Th2 cell lacks the ability to recruit into the skin. Other factors are therefore responsible for this.

GATA3 also has the property of "auto-activation", 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.