GATA transcription factor

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The GATA transcription factor family consists of six DNA-binding proteins (GATA1-6) that regulates transcription of DNA due to their ability to bind to the DNA sequence "GATA" which can therefore affect different diseases. [1] [2] [3]

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Transcription factor network (including GATA) involved in differentiation of the endoderm. Transcription factor network in endoderm induction..jpg
Transcription factor network (including GATA) involved in differentiation of the endoderm.

These six proteins are divided into two subfamilies of GATA1/2/3 and GATA4/5/6 based on differences in differentiation of stem cell tissues. [2] All six proteins are required for differentiating mesoderm derived tissues. The difference is that GATA1/2/3 is required in development and differentiation of ectoderm derived tissues (such as hematopoietic and the central nervous system), while GATA 4/5/6 is for differentiation of endoderm derived tissues (such as embryonic stem cells of the heart and skin. [2] Mutations in the GATA gene leads to problems in the thyroid, ears, kidney, heart, and can cause cancer. [2]  GATA can be used as biomarkers in predicting different diseases such as acute megakaryoblastic leukemia (AMKL) in Down syndrome, colorectal, and breast cancer. [2]

GATA transcription factors have been correlated to their broader influence on stem cell development. Findings however, have pointed to a more direct influence by GATA transcription factors, as they are salient components in the more concentrated regulation of gene expression. Data points to the roles GATA transcription factors play in stages past early development in endocrine organs. [4]

Molecular structure of the GATA transcription factor family

In non-vertebrates, the GATA genes are located close together on the chromosomes. Due to evolution, these genes in humans moved apart and are separated into 6 distinct chromosomal regions. [2] To regulate transcription of DNA, GATA transcription factors containing the class IV zinc finger motif look for GATA sites in DNA with two conserved zinc finger involved in long range DNA interactions. [3] [5] In non-vertebrates, GATA transcription factors contain one zinc finger DNA binding domain (ZNI). In humans, GATA transcription factors contain two zinc finger DNA binding domains (ZNI and ZNII) which looks for adenine or thymine before the GATA sequence and adenine or guanine after as shown by the schematic: (A/T)GATA(A/G). [2] Generally, ZNI and ZNII follow the sequence: CX2CX17–18CX2C. [2] [3] 70% of the regions in the zinc finger domains are the same while the terminal amino and carboxyl domains can change. [2]

Genes

In humans:

In yeast:

Role in breast cancer

Despite GATA’s influence on endocrine organs and cell development, they have a complex relation to the development and growth of breast cancer. Its immediate influence is not yet known, its high risk for mutation however, makes determining the immediate influence of paramount importance in battling breast cancer. [6]

Some research that has been done on the GATA transcription factor for its role in the development of breast cancer suggests that a specific GATA transcription factor GATA3 can actually inhibit further growth of breast cancer cells. [7] The complete mechanism in which this happens is still not clear. [7] However, research has suggested that the GATA transcription factor creates an unfavorable chemical environment for the breast cancer tumor cells which inhibits the progression of these cells. [7] One way that has been suggested is that the GATA transcription factor lowers the level of adenosine triphosphate (ATP) in the cell. [7] This creates an unfavorable chemical environment for the breast cancer cells because usually they require high levels of ATP to survive. [7] In addition, research has suggested that there is a specific gene called the TRP1 that is expressed in breast cancer cells and the GATA3 transcription factor plays a role in regulating this gene. [8]

Related Research Articles

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">EGR1</span> Protein-coding gene in the species Homo sapiens

EGR-1 also known as ZNF268 or NGFI-A is a protein that in humans is encoded by the EGR1 gene.

<span class="mw-page-title-main">GATA1</span> Protein-coding gene in humans

GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.

<span class="mw-page-title-main">AP-1 transcription factor</span> Instance of defined set in Homo sapiens with Reactome ID (R-HSA-6806560)

Activator protein 1 (AP-1) is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. AP-1 controls a number of cellular processes including differentiation, proliferation, and apoptosis. The structure of AP-1 is a heterodimer composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families.

<span class="mw-page-title-main">Mef2</span> Protein family

In the field of molecular biology, myocyte enhancer factor-2 (Mef2) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2 proteins mediate the stress response in some tissues. Mef2 proteins contain both MADS-box and Mef2 DNA-binding domains.

<span class="mw-page-title-main">RAR-related orphan receptor alpha</span> Protein-coding gene in the species Homo sapiens

RAR-related orphan receptor alpha (RORα), also known as NR1F1 is a nuclear receptor that in humans is encoded by the RORA gene. RORα participates in the transcriptional regulation of some genes involved in circadian rhythm. In mice, RORα is essential for development of cerebellum through direct regulation of genes expressed in Purkinje cells. It also plays an essential role in the development of type 2 innate lymphoid cells (ILC2) and mutant animals are ILC2 deficient. In addition, although present in normal numbers, the ILC3 and Th17 cells from RORα deficient mice are defective for cytokine production.

<span class="mw-page-title-main">GATA4</span> Protein-coding gene in the species Homo sapiens

Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.

<span class="mw-page-title-main">TRIM28</span> Protein-coding gene in the species Homo sapiens

Tripartite motif-containing 28 (TRIM28), also known as transcriptional intermediary factor 1β (TIF1β) and KAP1, is a protein that in humans is encoded by the TRIM28 gene.

<span class="mw-page-title-main">GATA2</span> Protein-coding gene in the species Homo sapiens

GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. GATA2 is encoded by the GATA2 gene, a gene which often suffers germline and somatic mutations which lead to a wide range of familial and sporadic diseases, respectively. The gene and its product are targets for the treatment of these diseases.

<span class="mw-page-title-main">LMO2</span> Protein-coding gene in the species Homo sapiens

LIM domain only 2, also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene.

<span class="mw-page-title-main">ID1</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein inhibitor ID-1 is a protein that in humans is encoded by the ID1 gene.

<span class="mw-page-title-main">GATA3</span> Protein-coding gene in the species Homo sapiens

GATA3 is a transcription factor that in humans is encoded by the GATA3 gene. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes.

<span class="mw-page-title-main">GATA6</span> Protein-coding gene in the species Homo sapiens

Transcription factor GATA-6, also known as GATA-binding factor 6 (GATA6), is protein that in humans is encoded by the GATA6 gene. The gene product preferentially binds (A/T/C)GAT(A/T)(A) of the consensus binding sequence.

<span class="mw-page-title-main">TEAD1</span> Protein-coding gene in the species Homo sapiens

Transcriptional enhancer factor TEF-1 also known as TEA domain family member 1 (TEAD1) and transcription factor 13 (TCF-13) is a protein that in humans is encoded by the TEAD1 gene. TEAD1 was the first member of the TEAD family of transcription factors to be identified.

<span class="mw-page-title-main">GATA5</span> Protein-coding gene in the species Homo sapiens

Transcription factor GATA-5 is a protein that in humans is encoded by the GATA5 gene.

<span class="mw-page-title-main">ZFPM2</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein ZFPM2, i.e. zinc finger protein, FOG family member 2, but also termed Friend of GATA2, Friend of GATA-2, FOG2, or FOG-2, is a protein that in humans is encoded by the ZFPM2 and in mice by the Zfpm2 gene.

<span class="mw-page-title-main">ZBTB32</span> Protein-coding gene in the species Homo sapiens

Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins, and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.

<span class="mw-page-title-main">FOXA1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.

<span class="mw-page-title-main">GATA zinc finger</span>

In molecular biology, GATA zinc fingers are zinc-containing domains found in a number of transcription factors. Some members of this class of zinc fingers specifically bind the DNA sequence (A/T)GATA(A/G) in the regulatory regions of genes., giving rise to the name of the domain. In these domains, a single zinc ion is coordinated by 4 cysteine residues. NMR studies have shown the core of the Znf to comprise 2 irregular anti-parallel beta-sheets and an alpha-helix, followed by a long loop to the C-terminal end of the finger. The N-terminal part, which includes the helix, is similar in structure, but not sequence, to the N-terminal zinc module of the glucocorticoid receptor DNA-binding domain. The helix and the loop connecting the 2 beta-sheets interact with the major groove of the DNA, while the C-terminal tail wraps around into the minor groove. Interactions between the Znf and DNA are mainly hydrophobic, explaining the preponderance of thymines in the binding site; a large number of interactions with the phosphate backbone have also been observed. Two GATA zinc fingers are found in GATA-family transcription factors. However, there are several proteins that only contain a single copy of the domain. It is also worth noting that many GATA-type Znfs have not been experimentally demonstrated to be DNA-binding domains. Furthermore, several GATA-type Znfs have been demonstrated to act as protein-recognition domains. For example, the N-terminal Znf of GATA1 binds specifically to a zinc finger from the transcriptional coregulator FOG1 (ZFPM1).

Pioneer factors are transcription factors that can directly bind condensed chromatin. They can have positive and negative effects on transcription and are important in recruiting other transcription factors and histone modification enzymes as well as controlling DNA methylation. They were first discovered in 2002 as factors capable of binding to target sites on nucleosomal DNA in compacted chromatin and endowing competency for gene activity during hepatogenesis. Pioneer factors are involved in initiating cell differentiation and activation of cell-specific genes. This property is observed in histone fold-domain containing transcription factors and other transcription factors that use zinc finger(s) for DNA binding.

References

  1. ↑ Ko LJ, Engel JD (July 1993). "DNA-binding specificities of the GATA transcription factor family". Molecular and Cellular Biology. 13 (7): 4011–4022. doi:10.1128/mcb.13.7.4011. PMC   359950 . PMID   8321208.
  2. 1 2 3 4 5 6 7 8 9 Lentjes, Marjolein HFM; Niessen, Hanneke EC; Akiyama, Yoshimitsu; de Bruïne, Adriaan P; Melotte, Veerle; van Engeland, Manon (2016). "The emerging role of GATA transcription factors in development and disease". Expert Reviews in Molecular Medicine. 18: e3. doi:10.1017/erm.2016.2. ISSN   1462-3994. PMC   4836206 . PMID   26953528.
  3. 1 2 3 Lowry, Jason A.; Atchley, William R. (17 September 1999). "Molecular Evolution of the GATA Family of Transcription Factors: Conservation Within the DNA-Binding Domain". Journal of Molecular Evolution. 50 (2): 103–115 – via Springer Link.
  4. ↑ Viger RS, Guittot SM, Anttonen M, Wilson DB, Heikinheimo M (April 2008). "Role of the GATA family of transcription factors in endocrine development, function, and disease". Molecular Endocrinology. 22 (4): 781–798. doi: 10.1210/me.2007-0513 . PMC   2276466 . PMID   18174356.
  5. ↑ Chen, Yongheng; Bates, Darren L.; Dey, Raja; Chen, Po-Han; Machado, Ana Carolina Dantas; Laird-Offringa, Ite A.; Rohs, Remo; Chen, Lin (November 2012). "DNA Binding by GATA Transcription Factor Suggests Mechanisms of DNA Looping and Long-Range Gene Regulation". Cell Reports. 2 (5): 1197–1206. doi:10.1016/j.celrep.2012.10.012. PMC   3978094 . PMID   23142663.
  6. ↑ Du F, Yuan P, Wang T, Zhao J, Zhao Z, Luo Y, Xu B (November 2015). "The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review". Medicinal Research Reviews. 35 (6): 1300–1315. doi:10.1002/med.21362. PMID   26313026. S2CID   11668034.
  7. 1 2 3 4 5 Li M, Qi Y, Chen M, Wang Z, Zeng D, Xiao Y, et al. (2019). "GATA Binding Protein 3 Boosts Extracellular ATP Hydrolysis and Inhibits Metastasis of Breast Cancer by Up-regulating Ectonucleoside Triphosphate Diphosphohydrolase 3". International Journal of Biological Sciences. 15 (12): 2522–2537. doi:10.7150/ijbs.35563. PMC   6854379 . PMID   31754326.
  8. ↑ Chen JQ, Bao Y, Lee J, Murray JL, Litton JK, Xiao L, et al. (October 2013). "Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer". Annals of Oncology. 24 (10): 2534–2542. doi:10.1093/annonc/mdt190. PMC   3784330 . PMID   23729783.
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