Disease relevance of GATA2

• By contrast, GATA2 overexpression is sufficient to force such cells and neuroblastoma cells to stop dividing but not to drive either type of cell into differentiation [1].
• Phosphorylation of GATA2 by Akt increases adipose tissue differentiation and reduces adipose tissue-related inflammation: a novel pathway linking obesity to atherosclerosis [2].
• Mutation analysis in the candidate Möbius syndrome genes PGT and GATA2 on chromosome 3 and EGR2 on chromosome 10 [3].
• GATA-2 can also physically associate with the PLZF-RARalpha fusion protein generated by the t(11;17) chromosomal translocation associated with acute promyelocytic leukemia (APL) [4].
• Regulation of the ET-1 promoter by hypoxia in non-endothelial cells required overexpression of GATA-2 and HIF-1alpha [5].

High impact information on GATA2

• By gene targeting in mouse embryonic stem cells, we demonstrate that the transcription factor GATA-2 plays a critical role in haematopoiesis, particularly of an adult type [6].
• Using a variety of experimental strategies, genes such as SCL, GATA-2, HoxB4, Flk-2, c-mpl, dlk, and others have been implicated as important regulators of stem cell growth [7].
• When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner [8].
• Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner [8].
• Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells [8].

Chemical compound and disease context of GATA2

• In conclusion, promoter I.7 is a GATA-2-regulated endothelial promoter of the human CYP19 gene and may increase estrogen biosynthesis in vascular endothelial cells of breast cancer [9].

Biological context of GATA2

• Chip assay revealed that SP1, AP2, and GATA2 bound the enhancer in BE2 cells [10].
• Transfection of GATA2 alone or with Ets, which binds adjacent to GATA, resulted in differentiation of BE2 cells in parallel with increased PDGF beta-receptor expression [10].
• Direct measurement of mRNAs showed increased gene expression of both types of transcription factors in chondroinduced hDFs, including NFKB2 (290% of control), RELA (160%), and GATA2 (190%) [11].
• By electrophoretic mobility shift assay, both GATA2 and GATA3 proteins could bind weakly to the wild-type P2 -689 GATA binding site but not to the mutated site [12].
• Insulin-dependent phosphorylation of serine 401 impairs GATA2 translocation to the nucleus and its DNA binding activity [2].

Anatomical context of GATA2

• In this respect, we have studied the possible implication of GATA2, a transcription factor that is involved in several neuronal specification pathways, in the control of the proliferation of neural progenitors in the embryonic spinal cord [1].
• Consistently, GATA2 also controls the proliferation capacity of mouse embryonic neuroepithelial cells in culture [1].
• GATA2 is highly expressed in stem cells, and its expression dramatically decreases when erythroid and megakaryocytic differentiation proceeds [13].
• GATA2 and -3 mRNA levels increased markedly during spontaneous in vitro differentiation of human cytotrophoblast cells when the cytotrophoblast cells fused to form a syncytium [14].
• GATA2 was positive for 3/5 T-cell lines but negative for the other cell lines [15].

Associations of GATA2 with chemical compounds

• Retinoic acid treatment of endothelial cells results in down-regulation of GATA-2 expression as well as down-regulation of PPET-1 gene expression [16].
• Western-blot analysis of nuclear extracts from both the uninduced and HU-induced HEL cells revealed that the level of GATA-2 transcription factor decreased, whereas the level of GATA-1 transcription factor increased following the time of hydroxyurea induction [17].
• Essential Role of GATA2 in the Negative Regulation of Thyrotropin {beta} Gene by Thyroid Hormone and Its Receptors [18].
• Treatment of HL-60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes, whereas levels of GATA-2 mRNA remained relatively constant [19].
• Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression [20].

Physical interactions of GATA2

• Here we report that the promyelocytic leukemia zinc finger (PLZF) protein can interact with GATA-2 and can modify its transactivation capacity [4].
• Transactivation experiments utilizing human GATA-2 eukaryotic expression vectors indicate that the GATA-2 protein interacts with the endothelin-1 GATA sequence to increase transcription of reporter genes in both BAEC and HeLa cells [21].
• GATA motifs present in promoters of other genes bind GATA-2 transcription factor and thereby regulate their transcriptional expression [22].
• Here, we studied whether the three GATA motifs flanking the transcription initiation sites regulate TFPI gene expression in HepG2 and ECV304 cells by binding to the GATA-2 transcription factor [22].
• On the basis of these measurements, we show that TPA-induced arrest of erythroid differentiation is coupled with the upregulation of GATA-2 protein, as well as the downregulation of GATA-1 protein [23].

Regulatory relationships of GATA2

• GATA-1 directly represses Gata2 transcription, and reduced GATA-2 synthesis promotes red blood cell development [24].
• Although GATA-2 regulates hematopoietic stem cell function, mechanisms controlling GATA-2 expression are undefined [25].
• Stimulation of GATA-2 as a mechanism of hydrogen peroxide suppression in hypoxia-induced erythropoietin gene expression [26].
• We have previously reported that expression of the human ET-1 gene is positively regulated by a cooperative interaction between GATA-2 and AP-1 transcription factors in cultured endothelial cells, however these factors are not sufficient to mediate cell type-specific expression [27].
• Our results suggest that it is the precise quantitative balance of GATA-1 and GATA-2 protein that regulates erythroid differentiation [23].

Other interactions of GATA2

• Cotransfection of hGATA-2 or hGATA-3 into alpha T3-1 cells activates the alpha-subunit gene threefold [28].
• A complex of a GATA-containing probe and recombinant GATA-2 expressed in COS cells comigrates with that present in gel shift experiments with nuclear extract derived from endothelial cells [16].
• Finally, PU.1 protein can inhibit both GATA-1 and GATA-2 transactivation function [29].
• Through a functional analysis, we demonstrate that PIASy potently suppresses the activity of the GATA-2-dependent human ET-1 promoter in endothelial cells [30].
• This induction involves two key events: increase of EPO-R and the decrease of GATA2 expression [31].

Analytical, diagnostic and therapeutic context of GATA2

• Sequence analysis of this fragment revealed the presence of candidate transcription factor-binding sequences for H-APF-1, SP1, GATA2, and the c-Myc proto-oncogene [32].
• RT-PCR analysis demonstrated that (1) GATA-1 expression significantly increased during gestation; (2) GATA-2 expression peaked at the onset of medullary haematopoiesis, declined thereafter, and remained at a constant level after 30 weeks post conception; and (3) GATA-3 expression revealed no changes during development [33].
• Using chromatin immunoprecipitation analysis, we show that GATA-1 binds a highly restricted upstream region of the approximately 70-kb GATA-2 domain, despite >80 GATA sites throughout the domain [25].
• In this report, we performed specific and quantitative measurements of GATA-1 and GATA-2 protein in a new erythroid cell line, SAM-1, after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) [23].
• We have categorized these blood mutants into four phenotypic classes based on analyses of whole embryos and isolated blood cells, as well as by in situ hybridization using the hematopoietic transcription factors GATA-1 and GATA-2 [34].

References