Alternative titles; symbols
HGNC Approved Gene Symbol: GATA3
SNOMEDCT: 724282009;
Cytogenetic location: 10p14 Genomic coordinates (GRCh38): 10:8,045,333-8,075,198 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10p14 | Hypoparathyroidism, sensorineural deafness, and renal dysplasia | 146255 | Autosomal dominant | 3 |
The genes for all 4 subunits of the T-cell antigen receptor (see 186880) are controlled by distinct enhancers and their enhancer-binding proteins. Marine and Winoto (1991) identified a common TCR regulatory element by demonstrating binding of the enhancer-binding protein GATA3 to the enhancer elements of all 4 TCR genes. GATA3 had been shown in the chicken to be an enhancer-binding protein containing a zinc finger domain. GATA3 mRNA was demonstrated by Northern blot analysis in T cells but not in B cells, macrophages, or HeLa cell lines. GATA3 was abundantly expressed in the T-lymphocyte lineage and was thought to participate in T-cell receptor gene activation through binding to enhancers. Labastie et al. (1994) cloned the human gene and the 5-prime end of the mouse gene. The 2 zinc fingers of GATA3 are encoded by 2 separate exons highly conserved with those of GATA1 (305371), but no other structural homologies between the 2 genes could be found.
Using LacZ reporter analysis, Asselin-Labat et al. (2007) found that Gata3 expression was restricted to ductal and alveolar luminal cells in mouse mammary gland. Western blot analysis showed that Gata3 expression was relatively high throughout different stages of mouse mammary development.
Labastie et al. (1994) determined that the human GATA3 gene contains 6 exons distributed over 17 kb of DNA.
Joulin et al. (1991) mapped the human GATA3 gene to chromosome 10p15 by in situ hybridization, and Copeland et al. (1993) mapped the mouse Gata3 gene to chromosome 2.
CD4 (186940) T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. Zheng and Flavell (1997) found that GATA3 was expressed at a high level in naive, freshly activated cells and Th2 lineage cells, but subsided to a minimal level in Th1 lineage cells as naive cells committed to their Th subset. Antisense GATA3 inhibited the expression of all Th2 cytokine genes in a Th2 clone. In transgenic mice, elevated GATA3 and CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, Zheng and Flavell (1997) concluded that GATA3 is necessary and sufficient for Th2 cytokine gene expression.
Interleukin-5 (IL5; 147850) plays a central role in the growth and differentiation of eosinophils and contributes to several disease states, including asthma. There is evidence for a role for cyclic AMP as an immunomodulator: agents that increase intracellular cAMP levels inhibit production of cytokines predominantly produced by T-alpha-1 (Th1) cells such as IL2 (147680) and interferon-gamma (IFNG; 147570). In contrast, the production of IL5, predominantly produced by Th2 cells, is enhanced by these agents. Siegel et al. (1995) defined precisely the cis-activating elements that regulate inducible murine Il5 transcription: sequences within the CLE0 element and also a region located between -70 and -59 of the IL5 promoter that binds the transcription factor Gata3. They speculated that activation via this unique sequence combination confers the specificity needed for selective expression of the IL5 gene in response to elevated levels of intracellular cAMP.
Zhang et al. (1997) demonstrated that GATA3 is critical for expression of the IL5 gene in Th2 cells. Whereas mutations in the GATA3 site abolished antigen- or cAMP-stimulated IL5 promoter activation in Th2 cells, ectopic expression of GATA3 in Th1 cells or in a nonlymphoid, non-IL5-producing cell line activated the IL5 promoter. Other findings suggested that GATA3 gene expression may play an important role in the balance between Th1 and Th2 subsets in immune responses. Zhang et al. (1997) suggested that inhibition of GATA3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases.
Zhang et al. (1998) showed that ectopic expression of GATA3 is sufficient to drive IL5 but not IL4 gene (147780) expression. Also, in Th2 cells, antisense GATA3 RNA inhibits IL5 but not IL4 promoter activation. The induction of IL5 gene expression by GATA3 involves high affinity binding of GATA3 to an inverted GATA repeat in the IL5 promoter.
Nakamura et al. (1999) found increased GATA3 gene expression in association with cells showing an increase in IL5 mRNA in asthmatic airways. They interpreted these findings as supporting a causal association between augmented GATA3 expression and dysregulated IL5 expression in atopic asthma.
Tong et al. (2000) showed that murine Gata2 and Gata3 are specifically expressed in white adipocyte precursors and that their downregulation sets the stage for terminal differentiation. Constitutive Gata2 and Gata3 expression suppressed adipocyte differentiation and trapped cells at the preadipocyte stage. This effect was mediated, at least in part, through the direct suppression of the peroxisome proliferator-activated receptor-gamma (PPARG; 601487). Gata3-deficient embryonic stem cells exhibit an enhanced capacity to differentiate into adipocytes, and defective Gata2 and Gata3 expression is associated with obesity. Thus, Tong et al. (2000) concluded that GATA2 and GATA3 regulate adipocyte differentiation through molecular control of the preadipocyte-adipocyte transition.
Fields et al. (2002) noted that high levels of histone acetylation at particular loci correlate with transcriptional activity, whereas reduced levels correlate with silencing. Using chromatin immunoprecipitation (ChIP), PCR, and green fluorescent protein analysis, they demonstrated that histones in the cytokine loci (IFNG and IL4) of naive T cells are unacetylated, but upon TCR stimulation, the loci are rapidly and progressively acetylated on histones H3 and H4. The acetylation at the IL4 locus occurs early, regardless of Th1/Th2 polarizing conditions, correlating with early transcription. The maintenance of acetylation depends on cytokine and STAT4 (600558) and STAT6 (601512) signaling and also on the transactivator activity of TBET (604895) and GATA3, the putative 'master regulators' of Th lineage determination.
Hwang et al. (2005) reported that TBET represses Th2 lineage commitment through tyrosine kinase-mediated interaction between itself and GATA3 that interferes with the binding of GATA3 to its target DNA. Hwang et al. (2005) concluded that their results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell. Hwang et al. (2005) showed that TBET phosphorylation is restricted to the TEC kinases ITK (186973) and RLK (600058). Coexpression studies demonstrated that this was most efficiently performed by ITK. In primary CD4 T cells isolated from ITK-, RLK-, or double ITK/RLK-deficient mice, the greatest diminution of TBET tyrosine phosphorylation was seen in the absence of ITK. Furthermore, mutation of TBET at tyrosine residue 525, but not control tyrosine residue 437, resulted in greatly reduced phosphorylation by ITK, revealing that ITK phosphorylates TBET at residue Y525 after T cell receptor stimulation.
Chen et al. (2006) noted that activated T cells, particularly Th1 cells, express sialyl Lewis x, but resting T cells do not. Using reporter analysis, they showed that TBET promoted and GATA3 repressed transcription of FUT7 (602030), the rate-limiting enzyme for sialyl Lewis x synthesis. TBET interfered with GATA3 binding to its target DNA, but GATA3 also interfered with TBET binding to the FUT7 promoter. GATA3 regulated FUT7 transcription by recruiting, in a phosphorylation-dependent manner, histone deacetylase-3 (HDAC3; 605166) and HDAC5 (605315) and by competing with CBP (CREBBP; 600140)/p300 (EP300; 602700) in binding to the N terminus of TBET. Maximal expression of FUT7 and sialyl Lewis x in T cells was obtained by ROG (ZBTB32; 605859)-mediated suppression of GATA3. Chen et al. (2006) concluded that the GATA3/TBET transcription factor complex regulates cell lineage-specific expression of lymphocyte homing receptors and that glycoconjugates are regulated by this complex to attain cell lineage-specific expression in Th1 and Th2 lymphocyte subsets.
Terminal deletions of chromosome 10p result in a DiGeorge (188400)-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness, and renal malformations. One region that contributes to this complex phenotype is that for the syndrome of hypoparathyroidism, sensorineural deafness, and renal insufficiency (HDRS; 146255). Van Esch et al. (2000) performed deletion-mapping studies in 2 HDRS patients and defined a critical 200-kb region that contains the GATA3 gene. Search for GATA3 mutations in 3 other HDRS probands identified 1 nonsense mutation (131320.0005) and 2 intragenic deletions (131320.0003, 131320.0004) that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results demonstrated that GATA3 is essential in the embryonic development of the parathyroids, auditory system, and kidneys, and showed that GATA3 haploinsufficiency causes human HDR syndrome.
Muroya et al. (2001) studied 9 Japanese families with HDR syndrome. FISH and microsatellite analysis showed heterozygous deletions including GATA3 in 4 families. Sequence analysis showed heterozygous novel mutations in 3 families, including a missense mutation in exon 4 (131320.0006), an insertion mutation (131320.0007), and a nonsense mutation in exon 6 (131320.0008).
In 10 patients with HDR syndrome from 7 unrelated families, Nesbit et al. (2004) identified and characterized 7 mutations in exons 3 through 6 of the GATA3 gene. Using electrophoretic mobility shift, dissociation, yeast 2-hybrid, and glutathione S-transferase pull-down assays, Nesbit et al. (2004) demonstrated that mutations involving the C-terminal zinc finger (ZnF2) or adjacent basic amino acids result in a loss of DNA binding, but those of the N-terminal zinc finger (ZnF1) either lead to a loss of interaction with specific zinc finger proteins of FOG2 (ZFPM2; 603693) or alter DNA-binding affinity.
Hernandez et al. (2007) reported a mother and daughter with HDRS and female genital tract malformations in whom they identified a deletion in the GATA3 gene (131320.0009).
Chiu et al. (2006) sequenced the CASR (601199) and GATA3 genes in 5 unrelated Chinese families with familial hypoparathyroidism. They identified 3 novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness. Except for a previously described polymorphism, they found no genetic variants in the CASR gene.
Ali et al. (2007) analyzed the GATA3 gene in 21 HDRS probands and 14 patients with isolated hypoparathyroidism (see FIH, 146200); no mutations were found in the FIH patients, but 13 different heterozygous germline mutations were identified in the HDRS probands, including 1 missense, 1 splice site, 3 nonsense, and 8 frameshift mutations. EMSA analysis revealed 3 classes of GATA3 mutations: those involving of loss of DNA binding due to loss of the C-terminal zinc finger, which represent over 90% of mutations reported in GATA3; those resulting in reduced DNA-binding affinity; and those that do not alter DNA binding or affinity but likely alter the conformation change that occurs during binding in the DNA major groove, as predicted by 3-dimensional modeling.
In a 14-year-old boy with neurologic symptoms in addition to the HDR triad of hypoparathyroidism, sensorineural deafness, and renal dysplasia, who did not have any microdeletion in the 22q11.2 or 10p14 regions by FISH analysis, Ferraris et al. (2009) identified a heterozygous de novo 2-bp deletion (131320.0013) in exon2 of the GATA3 gene. The authors concluded that haploinsufficiency of GATA3 may be responsible for a complex neurologic picture in addition to the known triad of HDR syndrome.
In a 29-year-old Portuguese with severe hypoparathyroidism, bilateral mild neurosensory deafness, and agenesis of the vagina and uterus but no kidney abnormalities, Moldovan et al. (2011) analyzed the GATA3 gene and identified a heterozygous missense mutation (C342Y; 131320.0014). The authors noted that this patient, along with the mother and daughter with HDR syndrome and female genital tract malformations studied by Hernandez et al. (2007), seemed to confirm the role of GATA3 in regulating developmental mechanisms of the uterus and vagina.
In a 52-year-old Japanese man with HDR, Kamezaki et al. (2017) identified heterozygosity for a missense mutation in the GATA3 gene (C288Y; 131320.0015). The mutation, which was identified by direct gene sequencing, was also identified in 4 other affected family members across 3 generations. In addition to hearing loss and hypoparathyroidism, the patient also had membranoproliferative glomerulonephritis-like findings on renal histology. Kamezaki et al. (2017) hypothesized that the glomerular abnormalities could be attributed to an imbalance of T-helper cells.
Chenouard et al. (2013) identified heterozygosity for a frameshift mutation in the GATA3 gene (131320.0016) in a patient with HDR. The mutation was identified by direct gene sequencing. Functional studies were not performed.
Lim et al. (2000) found that null mutations of Gata3 in mice led to a reduced accumulation of tyrosine hydroxylase (TH; 191290) and dopamine beta-hydroxylase (DPH; 223360) mRNA, whereas several other sympathetic nervous system (SNS) genes were unaffected. They showed that Th and Dbh deficiencies led to reduced noradrenalin in the SNS, and that noradrenaline deficiency was the proximal cause of death in mutants by feeding catechol intermediates to pregnant dams, thereby partially averting Gata3 mutation-induced lethality. The older, pharmacologically rescued mutants showed abnormalities that could not be detected in untreated mutants. These late embryonic defects included renal hypoplasia and developmental defects in structures derived from cephalic neural crest cells. Thus, Lim et al. (2000) showed that Gata3 has a role in the differentiation of multiple cell lineages during embryogenesis.
To elucidate GATA3 function, Pandolfi et al. (1995) disrupted the mouse gene by homologous recombination in embryonic stem cells. Mice heterozygous for the Gata3 mutation were found to be fertile and appeared in all respects to be normal, whereas homozygous mutant embryos died between days 11 and 12 postcoitum and displayed massive internal bleeding, marked growth retardation, severe deformities of the brain and spinal cord, and gross aberrations in fetal liver hematopoiesis. The functions of GATA1 and GATA2 (137295) had previously been studied by comparable methods. The results in aggregate demonstrated that each GATA-binding protein has a unique and essential function during the development of the mouse embryo. In each case, targeted mutagenesis also revealed surprising roles for each factor, underscoring the power of this experimental approach: GATA1 is essential for erythroid cell development, while disruption of GATA2 indicates a function during very early events in the development of all blood cell lineages.
Using microarray analysis, Kaufman et al. (2003) identified Gata3 as an induced transcription factor in embryonic day-13 to -18.5 mouse skin. Whole-mount in situ hybridization analysis revealed Gata3 expression in early vibrissae follicles and later in developing epidermis and in the cone of presumptive inner root sheath (IRS) precursor cells within hair follicles. Examination of pharmacologically rescued Gata3 -/- embryos and grafted Gata3 -/- skin showed aberrations in hair follicle morphogenesis that included not only structural defects in the IRS and hair shaft, but also molecular defects in cell lineage determination. Kaufman et al. (2003) concluded that, along with LEF1 (153245) and WNTs (see 164820), GATA3 is at the crossroads of both lymphocyte differentiation and of the IRS versus hair shaft cell fate decision in hair follicle morphogenesis.
Pai et al. (2003) generated mice conditionally lacking Gata3 at early (double-negative) and late (double-positive) stages of thymic differentiation. They found that Gata3 was indispensable for thymocytes to pass through beta selection, the process by which T-cell receptor-beta is paired with pre-T-cell receptor-alpha, a requirement for double-negative stage-3 cell survival. Furthermore, Gata3 was required for single-positive Cd4 thymocyte development. Pai et al. (2003) concluded that continued expression of GATA3 is required at multiple stages of thymocyte differentiation.
Zhu et al. (2004) generated mice with a conditional deletion of Gata3 and Gata3-deficient mouse T-cell lines and found that both Il4-dependent and -independent Th2 differentiation was diminished, permitting Th1 differentiation in the absence of Ifng and Il12 (see 161561). Deletion of Gata3 from established Th2 cells abolished production of Il5 and Il13 (147683), but not of Il4. Mice lacking Gata3 produced Ifng rather than Th2 cytokines in response to infection with Nippostrongylus brasiliensis. Zhu et al. (2004) concluded that Gata3 serves as a principal switch in determining Th1-Th2 responses.
Van der Wees et al. (2004) analyzed auditory brainstem response thresholds in heterozygous Gata3-knockout mice from 1 to 19 months of age and demonstrated a hearing loss of 30 dB compared to wildtype littermates. No physiologic or morphologic abnormalities were found in the brainstem, cerebral cortex, or the outer or middle ear. However, the cochleae of Gata3 +/- mice showed significant progressive morphologic degeneration starting with the outer hair cells at the apex and ultimately involving all hair cells and supporting cells in the entire cochlea. Van der Wees et al. (2004) concluded that hearing loss following GATA3 haploinsufficiency is peripheral in nature and that this defect is detectable from early postnatal development and continues through adulthood.
Kouros-Mehr et al. (2006) found that Gata3 was the most highly enriched transcription factor in mammary epithelium of pubertal mice. Conditional deletion of Gata3 led to severe defects in mammary development due to failure in terminal end bud formation during puberty. After acute Gata3 loss, adult mice exhibited undifferentiated luminal cell expansion with basement-membrane detachment, which led to caspase (see CASP1; 147678)-mediated cell death.
To examine the role of Gata3 in breast epithelial development, Asselin-Labat et al. (2007) conditionally deleted Gata3 at different stages of mouse development. Most mice with Gata3 deletion died shortly following birth, with only about 1 in 200 surviving. Survivors had hair loss, lacked mammary glands, and exhibited severely diminished mammary epithelial structures. Specific deletion of Gata3 in lobuloalveolar units that form during pregnancy resulted in impaired development of mammary glands, as lobuloalveolar units appeared substantially smaller and contained few lipid droplets. Gene expression analysis showed that differentiation toward alveolar luminal cells, 1 of the 3 epithelial cell types in mammary gland, was markedly reduced in Gata3-deficient mammary gland. High expression of Gata3 in the cultured mouse mammary stem cell-enriched subpopulation promoted differentiation along the alveolar cell lineage. The authors concluded that GATA3 functions as a key regulator of mammary cell specification and epithelial differentiation at multiple stages of mammary ontogeny.
Van Esch et al. (2000) detected deletion of 900 kb including the GATA3 gene in a patient with HDR syndrome (HDRS; 146255).
In 4 affected members of a family with HDR syndrome (HDRS; 146255), Van Esch et al. (2000) found a 250-kb deletion resulting in deletion of one allele of the GATA3 gene.
Van Esch et al. (2000) reported a patient with HDR syndrome (HDRS; 146255) with a deletional frameshift of 49 nucleotides in exon 3 of the GATA3 gene. This mutation was predicted to result in a truncated protein lacking both zinc fingers and thereby leading to GATA3 haploinsufficiency.
In a patient with HDR syndrome (HDRS; 146255), Van Esch et al. (2000) identified an in-frame deletion of codons 316 to 319, which resulted in loss of 4 amino acids (TSCA) and disruption of the C-terminal zinc finger domain, leading to GATA3 haploinsufficiency.
In a mother and her son with HDR syndrome (HDRS; 146255), Van Esch et al. (2000) identified a nonsense mutation at nucleotide 828 of the GATA3 gene, a C-to-T transition resulting in an arginine-to-ter substitution at residue 277 (R277X). This mutation was predicted to result in a truncated protein lacking both zinc fingers and thereby leading to GATA3 haploinsufficiency.
Muroya et al. (2001) identified a T-to-A transversion at nucleotide 823 in the first zinc finger domain of exon 4 of the GATA3 gene in a Japanese family with HDR syndrome (HDRS; 146255).
In a Japanese family with HDR syndrome (HDRS; 146255), Muroya et al. (2001) identified a 2-bp insertion at nucleotide 900 and a 3-bp insertion at nucleotide 901 in exon 4 of the GATA3 gene (900insAA plus 901insCCT, or C901AACCCT), resulting in premature termination at codon 357 with loss of the second zinc finger domain.
In a 33-year-old Japanese man who had hypoparathyroidism, wore hearing aids, and had proteinuria and hematuria (HDRS; 146255), Muroya et al. (2001) identified heterozygosity for a 1099C-T transition in exon 6 of the GATA3 gene, resulting in an arg367-to-ter (R367X) substitution. The mutation was also detected in his 3-year-old daughter, who did not have hypoparathyroidism or renal dysplasia, but was clinically suspected of hearing loss due to speech delay.
In an 18-year-old Han Chinese boy and his 5-year-old sister, who both had hypoparathyroidism and bilateral sensorineural deafness but no renal dysplasia, Sun et al. (2009) identified heterozygosity for the R367X mutation in the GATA3 gene. The mutation was not found in either of their unaffected parents; Sun et al. (2009) concluded that 1 of the parents likely had germinal mosaicism of the mutant GATA3 gene.
In a mother and daughter with HDR syndrome (HDRS; 146255), Hernandez et al. (2007) identified heterozygosity for a 1-bp deletion (431delG) in exon 3 of the GATA3 gene, causing a frameshift at codon 144 and resulting in a termination signal at codon 194. The mother had a nonfunctional right kidney and a septate uterus, whereas her daughter had right renal agenesis and uterus didelphys with septate vagina. The mutation was not found in the unaffected sister, father, or maternal aunt.
In affected members of a Chinese family with HDR syndrome (HDRS; 146255), Chiu et al. (2006) detected a single-base deletion at nucleotide 478 in exon 3 of the GATA3 gene (478delG), predicted to result in frameshift from codon 160 and premature termination at codon 194. The mutation was hypothesized to disrupt dual zinc fingers as well as 1 transactivating domain.
In affected members of a Chinese family with HDR syndrome (HDRS; 146255), Chiu et al. (2006) detected a donor splice site mutation at the GATA3 exon 4/intron 4 boundary (IVS4+2T-GCTTACTTCCC) that was predicted to lead to truncated GATA3 proteins lacking both N- and C-terminal zinc-containing fingers.
In affected members of a Chinese family with HDR syndrome (HDRS; 146255), Chiu et al. (2006) detected an A-to-T transversion at nucleotide 1059 in exon 6 of the GATA3 gene that resulted in an arg353-to-ser (R353S) substitution. The mutation was predicted to disrupt the helical turn and thus changed the angle between the C-terminal zinc finger and the adjacent C-terminal tail.
In a 14-year-old boy with neurologic symptoms in addition to hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDRS; 146255), Ferraris et al. (2009) identified heterozygosity for a de novo 2-bp deletion (108delGG) in exon 2 of the GATA3 gene, resulting in a frameshift and a premature stop codon after a new 15-amino acid sequence. The unaffected parents did not carry the mutation, which was also not found in 100 controls. Neurologic involvement included basal ganglia calcifications, palpebral ptosis, postural strabismus, horizontal nystagmus, and pseudopapilledema.
In a 29-year-old Portuguese woman with severe hypoparathyroidism, bilateral mild neurosensory deafness, and agenesis of the vagina and uterus but no kidney abnormalities (see 146255), Moldovan et al. (2011) identified heterozygosity for a 1025G-A transition in exon 5 of the GATA3 gene, resulting in a cys342-to-tyr (C342Y) substitution at a highly conserved residue within the functionally important zinc finger-2 domain. The parents were unavailable for study, but there was no family history of the disease.
In a 52-year-old Japanese man with HDR syndrome (HDRS; 146255), Kamezaki et al. (2017) identified heterozygosity for a C-to-G transversion in the GATA3 gene, resulting in a cys288-to-trp (C288W) substitution in the ZnF1 domain. The mutation, which was found by direct gene sequencing, was also identified in 4 other affected family members across 3 generations. In addition to hearing loss and hypoparathyroidism, the patient had membranoproliferative glomerulonephritis-like findings on renal histology.
In a patient with HDR syndrome (HDRS; 146255), Chenouard et al. (2013) identified heterozygosity for a 1-bp deletion (c.951delC) in exon 5 of the GATA3 gene, resulting in a frameshift and premature termination (Cys318ValfsTer38). The mutation, which was identified by direct gene sequencing, was not found in either parent. The patient had hypoparathyroidism, bilateral sensorineural hearing loss, nephrocalcinosis, and a glomerular nephropathy.
Ali, A., Christie, P. T., Grigorieva, I. V., Harding, B., Van Esch, H., Ahmed, S. F., Bitner-Glindzicz, M., Blind, E., Bloch, C., Christin, P., Clayton, P., Gecz, J. {and 16 others}: Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding by the GATA3 transcription factor. Hum. Molec. Genet. 16: 265-275, 2007. [PubMed: 17210674] [Full Text: https://doi.org/10.1093/hmg/ddl454]
Asselin-Labat, M.-L., Sutherland, K. D., Barker, H., Thomas, R., Shackleton, M., Forrest, N. C., Hartley, L., Robb, L., Grosveld, F. G., van der Wees, J., Lindeman, G. J., Visvader, J. E. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nature Cell Biol. 9: 201-209, 2007. [PubMed: 17187062] [Full Text: https://doi.org/10.1038/ncb1530]
Chen, G.-Y., Osada, H., Santamaria-Babi, L. F., Kannagi, R. Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Proc. Nat. Acad. Sci. 103: 16894-16899, 2006. [PubMed: 17075044] [Full Text: https://doi.org/10.1073/pnas.0607926103]
Chenouard, A., Isidor, B., Allain-Launay, E., Moreau, A., Le Bideau, M., Roussey, G. Renal phenotypic variability in HDR syndrome: glomerular nephropathy as a novel finding. Europ. J. Pediat. 172: 107-110, 2013. [PubMed: 23052618] [Full Text: https://doi.org/10.1007/s00431-012-1845-y]
Chiu, W.-Y., Chen, H.-W., Chao, H.-W., Yann, L.-T., Tsai, K.-S. Identification of three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population. J. Clin. Endocr. Metab. 91: 4587-4592, 2006. [PubMed: 16912130] [Full Text: https://doi.org/10.1210/jc.2006-0864]
Copeland, N. G., Jenkins, N. A., Gilbert, D. J., Eppig, J. T., Maltais, L. J., Miller, J. C., Dietrich, W. F., Weaver, A., Lincoln, S. E., Steen, R. G., Stein, L. D., Nadeau, J. H., Lander, E. S. A genetic linkage map of the mouse: current applications and future prospects. Science 262: 57-66, 1993. [PubMed: 8211130] [Full Text: https://doi.org/10.1126/science.8211130]
Ferraris, S., Del monaco, A. G., Garelli, E., Carando, A., De Vito, B., Pappi, P., Lala, R., Ponzone, A. HDR syndrome: a novel 'de novo' mutation in GATA3 gene. Am. J. Med. Genet. 149A: 770-775, 2009. [PubMed: 19248180] [Full Text: https://doi.org/10.1002/ajmg.a.32689]
Fields, P. E., Kim, S. T., Flavell, R. A. Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation. J. Immun. 169: 647-650, 2002. [PubMed: 12097365] [Full Text: https://doi.org/10.4049/jimmunol.169.2.647]
Hernandez, A. M., Villamar, M., Rosello, L., Moreno-Pelayo, M. A., Moreno, F., del Castillo, I. Novel mutation in the gene encoding the GATA3 transcription factor in a Spanish familial case of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome with female genital tract malformations. Am. J. Med. Genet. 143A: 757-762, 2007. [PubMed: 17309062] [Full Text: https://doi.org/10.1002/ajmg.a.31617]
Hwang, E. S., Szabo, S. J., Schwartzberg, P. L., Glimcher, L. H. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307: 430-433, 2005. [PubMed: 15662016] [Full Text: https://doi.org/10.1126/science.1103336]
Joulin, V., Bories, D., Eleout, J. F., Labastie, M. C., Chretien, S., Mattei, M. G., Romeo, P. H. A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J. 10: 1809-1816, 1991. [PubMed: 2050118] [Full Text: https://doi.org/10.1002/j.1460-2075.1991.tb07706.x]
Kamezaki, M., Kusaba, T., Adachi, T., Yamashita, N., Nakata, M., Ota, N., Shiotsu, Y., Ishida, M., Usui, T., Tamagaki, K. Unusual proliferative glomerulonephritis in a patient diagnosed to have hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome with a novel mutation in the GATA3 gene. Intern. Med. 56: 1393-1397, 2017. [PubMed: 28566604] [Full Text: https://doi.org/10.2169/internalmedicine.56.7930]
Kaufman, C. K., Zhou, P., Pasolli, H. A., Rendl, M., Bolotin, D., Lim, K.-C., Dai, X., Alegre, M.-L., Fuchs, E. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 17: 2108-2122, 2003. [PubMed: 12923059] [Full Text: https://doi.org/10.1101/gad.1115203]
Kouros-Mehr, H., Slorach, E. M., Sternlicht, M. D., Werb, Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell 127: 1041-1055, 2006. [PubMed: 17129787] [Full Text: https://doi.org/10.1016/j.cell.2006.09.048]
Labastie, M.-C., Bories, D., Chabret, C., Gregoire, J.-M., Chretien, S., Romeo, P.-H. Structure and expression of the human GATA3 gene. Genomics 21: 1-6, 1994. [PubMed: 8088776] [Full Text: https://doi.org/10.1006/geno.1994.1217]
Lim, K.-C., Lakshmanan, G., Crawford, S. E., Gu, Y., Grosveld, F., Engel, J. D. Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nature Genet. 25: 209-212, 2000. [PubMed: 10835639] [Full Text: https://doi.org/10.1038/76080]
Marine, J., Winoto, A. The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. Proc. Nat. Acad. Sci. 88: 7284-7288, 1991. [PubMed: 1871134] [Full Text: https://doi.org/10.1073/pnas.88.16.7284]
Moldovan, D., Carvalho, R., Jorge, Z., Medeira, A. A new case of HDR syndrome with severe female genital tract malformation: comment on 'Novel mutation in the gene encoding the GATA3 transcription factor in a Spanish familial case of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome with female genital tract malformations' by Hernandez et al. (Letter) Am. J. Med. Genet. 155A: 2329-2330, 2011. [PubMed: 21834031] [Full Text: https://doi.org/10.1002/ajmg.a.34153]
Muroya, K., Hasegawa, T., Ito, Y., Nagai, T., Isotani, H., Iwata, Y., Yamamoto, K., Fujimoto, S., Seishu, S., Fukushima, Y., Hasegawa, Y., Ogata, T. GATA3 abnormalities and the phenotypic spectrum of HDR syndrome. J. Med. Genet. 38: 374-380, 2001. [PubMed: 11389161] [Full Text: https://doi.org/10.1136/jmg.38.6.374]
Nakamura, Y., Ghaffar, O., Olivenstein, R., Taha, R. A., Soussi-Gounni, A., Zhang, D.-H., Ray, A., Hamid, Q. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J. Allergy Clin. Immun. 103: 215-222, 1999. [PubMed: 9949310] [Full Text: https://doi.org/10.1016/s0091-6749(99)70493-8]
Nesbit, M. A., Bowl, M. R., Harding, B., Ali, A., Ayala, A., Crowe, C., Dobbie, A., Hampson, G., Holdaway, I., Levine, M. A., McWilliams, R., Rigden, S., Sampson, J., Williams, A. J., Thakker, R. V. Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. J. Biol. Chem. 279: 22624-22634, 2004. [PubMed: 14985365] [Full Text: https://doi.org/10.1074/jbc.M401797200]
Pai, S.-Y., Truitt, M. L., Ting, C.-N., Leiden, J. M., Glimcher, L. H., Ho, I.-C. Critical roles for transcription factor GATA-3 in thymocyte development. Immunity 19: 863-875, 2003. [PubMed: 14670303] [Full Text: https://doi.org/10.1016/s1074-7613(03)00328-5]
Pandolfi, P. P., Roth, M. E., Karis, A., Leonard, M. W., Dzierzak, E., Grosveld, F. G., Engel, J. D., Lindenbaum, M. H. Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nature Genet. 11: 40-44, 1995. [PubMed: 7550312] [Full Text: https://doi.org/10.1038/ng0995-40]
Siegel, M. D., Zhang, D.-H., Ray, P., Ray, A. Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements. J. Biol. Chem. 270: 24548-24555, 1995. [PubMed: 7592673] [Full Text: https://doi.org/10.1074/jbc.270.41.24548]
Sun, Y., Xia, W., Xing, X., Li, M., Wang, O., Jiang, Y., Pei, Y., Ye, P., Liu, H., Hu, Y., Meng, X., Zhou, X. Germinal mosaicism of GATA3 in a family with HDR syndrome. Am. J. Med. Genet. 149A: 776-778, 2009. [PubMed: 19253381] [Full Text: https://doi.org/10.1002/ajmg.a.32706]
Tong, Q., Dalgin, G., Xu, H., Ting, C.-N., Leiden, J. M., Hotamisligil, G. S. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 290: 134-138, 2000. [PubMed: 11021798] [Full Text: https://doi.org/10.1126/science.290.5489.134]
van der Wees, J., van Looij, M. A. J., de Ruiter, M. M., Elias, H., van der Burg, H., Liem, S.-S., Kurek, D., Engel, J. D., Karis, A., van Zanten, B. G. A., De Zeeuw, C. I., Grosveld, F. G., van Doorninck, J. H. Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder. Neurobiol. Dis. 16: 169-178, 2004. [PubMed: 15207274] [Full Text: https://doi.org/10.1016/j.nbd.2004.02.004]
Van Esch, H., Groenen, P., Nesbit, M. A., Schuffenhauer, S., Lichtner, P., Vanderlinden, G., Harding, B., Beetz, R., Bilous, R. W., Holdaway, I., Shaw, N. J., Fryns, J.-P., Van de Ven, W., Thakker, R. V., Devriendt, K. GATA3 haplo-insufficiency causes human HDR syndrome. Nature 406: 419-422, 2000. [PubMed: 10935639] [Full Text: https://doi.org/10.1038/35019088]
Zhang, D.-H., Cohn, L., Ray, P., Bottomly, K., Ray, A. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272: 21597-21603, 1997. [PubMed: 9261181] [Full Text: https://doi.org/10.1074/jbc.272.34.21597]
Zhang, D.-H., Yang, L., Ray, A. Cutting edge: differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J. Immun. 161: 3817-3821, 1998. [PubMed: 9780145]
Zheng, W., Flavell, R. A. The transcription factor GATA-3 is necessary and sufficient for the Th2 cytokine gene expression in CD4 T cells. Cell 89: 587-596, 1997. [PubMed: 9160750] [Full Text: https://doi.org/10.1016/s0092-8674(00)80240-8]
Zhu, J., Min, B., Hu-Li, J., Watson, C. J., Grinberg, A., Wang, Q., Killeen, N., Urban, J. F., Jr., Guo, L., Paul, W. E. Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nature Immun. 5: 1157-1165, 2004. [PubMed: 15475959] [Full Text: https://doi.org/10.1038/ni1128]