| 2000 |
GATA3 haploinsufficiency causes HDR syndrome (hypoparathyroidism, sensorineural deafness, renal anomaly). Deletion mapping defined a critical 200 kb region containing GATA3; nonsense mutations and intragenic deletions in HDR patients predicted loss of function, confirmed by absence of DNA binding by the mutant GATA3 protein in binding assays. |
Deletion mapping, mutation analysis, DNA-binding assay with mutant GATA3 protein |
Nature |
High |
10935639
|
| 2013 |
GATA3 suppresses breast cancer metastasis and alters the tumor microenvironment by inducing microRNA-29b (miR-29b) expression; miR-29b targets pro-metastatic regulators including VEGFA, ANGPTL4, PDGF, LOX, MMP9, ITGA6, ITGB1, and TGFB. |
Overexpression/knockdown of GATA3 and miR-29b in breast cancer cells and mouse models; target gene identification by functional assays |
Nature Cell Biology |
High |
23354167
|
| 2007 |
Notch signaling directly regulates Gata3 transcription during Th2 cell differentiation. Activated Notch1 specifically and directly upregulates a developmentally regulated Gata3 transcript containing exon 1a sequences; Notch acts in parallel with GATA-3 to synergistically activate IL-4 expression. |
Activated Notch1 allele introduction into CD4+ T cells; transcript-specific analysis; genetic epistasis |
Immunity |
High |
17658278
|
| 2008 |
In human T lymphocytes, GATA3 is normally localized to the cytoplasm, but upon activation via TCR (CD3) and co-stimulatory receptor CD28, GATA3 is phosphorylated by p38 MAP kinase and translocates to the nucleus via the nuclear import protein importin-alpha. Corticosteroids bound to glucocorticoid receptors inhibit GATA3 function by competing for nuclear entry via importin-alpha and by inhibiting p38 MAP kinase through induction of MAP kinase phosphatase-1. |
Subcellular localization studies, kinase inhibitor assays, nuclear import pathway dissection |
Current Molecular Medicine |
Medium |
18691059
|
| 2013 |
p38 MAP kinase activation in natural helper (NH/ILC2) cells leads to phosphorylation of GATA3; the phosphorylated form of GATA3 binds to the IL-5 and IL-13 promoters. p38 inhibition blocks this phosphorylation and blocks IL-5, IL-13, and IL-6 production. Mature NH cells lacking Gata3 are impaired in proliferation and production of IL-5 and IL-13. |
p38 inhibitor (SB203580) treatment, ChIP showing phospho-GATA3 binding to IL-5/IL-13 promoters, conditional Gata3 knockout in NH cells |
Journal of Immunology |
High |
23851685
|
| 2008 |
Gfi1 (growth factor independent-1), a downstream target of the ERK MAPK cascade, stabilizes GATA3 protein in Th2 cells. In the absence of Gfi1, enhanced ubiquitin/proteasome-dependent degradation of GATA3 protein was observed; overexpression of GATA3 rescued Th2 cell functional defects in Gfi1-deficient cells. |
Gfi1 knockout T cells, ubiquitin-proteasome pathway analysis, GATA3 overexpression rescue experiments |
Journal of Biological Chemistry |
High |
18701459
|
| 2013 |
Gata3 associates with RuvB-like protein 2 (Ruvbl2) and directly represses expression of the CDK inhibitor Cdkn2c at its locus in an Ruvbl2-dependent manner, thereby facilitating Th2 cell proliferation. |
Co-immunoprecipitation of Gata3-Ruvbl2 complex, ChIP showing Gata3 binding to Cdkn2c locus, Cdkn2c knockdown rescue of Gata3-deficient proliferation defect |
PNAS |
High |
24167278
|
| 2017 |
GATA3 physically associates with HIF-1α under hypoxia to inhibit ubiquitination and proteasomal degradation of HIF-1α (independent of prolyl hydroxylation), thereby stabilizing HIF-1α. The GATA3/HIF-1α complex binds to and regulates HIF-1 target genes, enhancing cancer cell invasiveness. |
Co-IP of GATA3-HIF-1α, ubiquitination assay, ChIP showing GATA3/HIF-1α complex at target gene promoters, HIF-1α knockdown reversal of GATA3-mediated invasiveness |
Oncogene |
High |
28263977
|
| 2018 |
Bcl11b binds to GATA3 through protein-protein interaction and colocalizes with GATA3 at cis-regulatory elements in Th2 cells. The GATA3/Bcl11b complex limits Th2 cytokine (IL-4, IL-5, IL-13) expression; upregulation of these cytokines in Bcl11b-deficient Th2 cells is completely GATA3-dependent. |
Co-IP of Bcl11b-GATA3, ChIP-seq co-occupancy analysis, Bcl11b knockout with GATA3 dependence test, RNA-seq |
Journal of Experimental Medicine |
High |
29514917
|
| 2020 |
Sox12 promotes Fbw7-mediated ubiquitination and proteasomal degradation of GATA3 protein in Th2 cells without affecting GATA3 mRNA. Fbw7 knockdown partially abrogates Sox12-mediated GATA3 suppression, identifying Fbw7 as the E3 ligase responsible for GATA3 degradation. |
Sox12 overexpression/knockout, proteasome inhibitor assays, ubiquitination assay of GATA3, Fbw7 knockdown rescue |
Cellular & Molecular Immunology |
High |
32152552
|
| 2019 |
GATA3 recruits the chromatin-remodeling MLL4 complex and directly interacts with UTX (histone H3K27 demethylase), ASH2L, and RBBP5. The GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, controlling the EMT program; the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis. |
Co-IP of GATA3 with UTX/ASH2L/RBBP5, RNA-seq, ChIP-seq, in vitro and in vivo functional assays |
Cell Death & Disease |
High |
31685800
|
| 2018 |
GATA3 interacts with and is acetylated by the acetyltransferase CBP at lysine 119 (K119). Class I deacetylases HDAC1, HDAC2, and HDAC3 deacetylate GATA3. Acetylation-mimicking K119Q mutant GATA3 inhibits lung adenocarcinoma cell migration and invasion with concomitant downregulation of EMT transcription factors Slug, Zeb1, and Zeb2. |
Co-IP of GATA3-CBP interaction, mass spectrometry identification of acetylation site, HDAC deacetylation assay, acetylation-mimetic mutant functional assays |
Biochemical and Biophysical Research Communications |
High |
29453984
|
| 2021 |
BRCA1 depletion stimulates methylation of the GATA3 promoter, thereby repressing GATA3 transcription. GATA3 functions downstream of BRCA1 to suppress EMT in mammary tumor development; reconstitution of GATA3 in BRCA1-deficient tumor cells activates mesenchymal-epithelial transition and suppresses tumor initiation and metastasis. |
BRCA1/GATA3 depletion in human cells, promoter methylation analysis, genetically engineered mouse models, GATA3 reconstitution rescue experiments |
Theranostics |
High |
34373738
|
| 2016 |
GATA3 interacts with GCM1 through the DNA-binding domain and first transcriptional activation domain of GCM1, and through the transcriptional activation domains and zinc finger 1 domain of GATA3. GATA3 does not affect GCM1 DNA binding but suppresses GCM1 transcriptional activity, thereby reducing HtrA4 expression and inhibiting trophoblast cell invasion. |
Co-IP of GATA3-GCM1, domain mapping by deletion mutants, luciferase transcriptional activity assay, GATA3 knockdown in trophoblast cell lines |
Scientific Reports |
High |
26899996
|
| 2015 |
GATA3 suppresses adipogenesis by binding to the promoter of PPARγ and other key adipogenic regulators. AMPK activation by AICAR increases GATA3 expression through Wnt/β-catenin signaling: AMPK phosphorylates and inhibits GSK3β, stabilizing β-catenin, which then interacts with TCF to induce GATA3 transcription. AICAR also relieves CtBP co-repressor binding at the GATA3 promoter. |
ChIP showing GATA3 binding to PPARγ promoter, β-catenin/TCF reporter assay, AMPK/GSK3β phosphorylation assays, Wnt pathway inhibition |
Journal of Biological Chemistry |
High |
26109067
|
| 2004 |
In auditory neuroblasts, GATA3 knockdown via antisense oligonucleotides reversibly downregulates NeuroD expression, demonstrating that NeuroD expression is dependent on GATA3 in auditory neuroblasts. GATA3 and NeuroD mark distinct neuronal populations: at E13.5 most auditory neurons express GATA3 but not NeuroD, whereas vestibular neurons express NeuroD but not GATA3. |
Antisense oligonucleotide knockdown in conditionally immortal auditory neuroblast cell line; immunostaining and expression analysis in vivo |
Mechanisms of Development |
Medium |
15003631
|
| 2004 |
In Gata3-knockout mice, Gata2 expression is delayed and strongly reduced in the otic epithelium, indicating that Gata3 is required for normal Gata2 expression in the inner ear. Ear morphogenesis is blocked in Gata3-deficient embryos. |
Gata3 knockout mouse analysis, in situ hybridization and immunostaining for Gata2 expression in Gata3-/- embryos |
Developmental Dynamics |
Medium |
15499560
|
| 2014 |
Cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors is required for development of gut RORγt+ ILC3 subsets. Gata3-deficient chimeric mice lack all intestinal RORγt+ ILC3 subsets and show defective IL-22 production early after Citrobacter rodentium infection. |
Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors; flow cytometry; infection challenge model |
Journal of Experimental Medicine |
High |
24419270
|
| 2019 |
Gata3 directly targets Runx1 in stromal cells of the aorta-gonads-mesonephros (AGM) region, binding to specific enhancer elements at the Runx1 locus. This interaction promotes haematopoietic stem cell emergence in the embryo, with Runx1 expression reduced in Gata3-/- embryos. |
ChIP-seq and ChIP-on-chip in AGM-derived stromal cell line; co-localization by immunostaining; Gata3-/- embryo analysis |
IUBMB Life |
High |
31634421
|
| 2017 |
GATA3 knockdown in keratinocytes significantly reduces filaggrin (FLG) mRNA expression under atopic dermatitis-like inflammatory conditions; overexpression of GATA3 upregulates both filaggrin and filaggrin-2 (FLG2) mRNA expression, demonstrating GATA3 regulates epidermal barrier genes. |
shRNA knockdown and GATA3 overexpression in primary human keratinocytes; RT-qPCR |
Scientific Reports |
Medium |
28928464
|
| 2016 |
GATA3 knockdown in first trimester trophoblast cells (HTR8/SVneo) decreases cell migration and invasion. RNA-seq of GATA3 knockdown cells identified 96 differentially regulated genes including CTGF, CYR61, ADAMTS12, and TIMP3. Estradiol downregulates GATA3 expression in these cells. |
siRNA knockdown in trophoblast cell line, migration/invasion assays, RNA-seq, estradiol treatment |
Biology of Reproduction |
Medium |
27733378
|
| 2021 |
GATA3 mediates doxorubicin resistance by transcriptionally repressing CYB5R2, thereby maintaining iron homeostasis and inhibiting ferroptosis. ChIP and luciferase assays confirmed direct GATA3 regulation of CYB5R2 expression. |
GATA3 overexpression/knockdown, ChIP assay, luciferase reporter assay, iron/ROS/lipid peroxidation detection, in vivo xenograft |
Drug Resistance Updates |
High |
37230023
|
| 2022 |
p300-dependent acetylation regulates GATA3-mediated transcription in T-cell neoplasms by attenuating GATA3 DNA binding. |
Biochemical acetylation assays, DNA binding assays with acetylated GATA3 |
Blood Cancer Journal |
Medium |
36329027
|
| 2021 |
GATA3 disruption in mouse embryos leads to craniofacial microsomia and syngnathia (bony fusion of jaws), resulting from changes in BMP4 and FGF8 gene regulatory networks within neural crest cells near the maxillomandibular junction, demonstrating GATA3 is essential for establishing network factors that separate upper and lower jaw patterning domains. |
Conditional Gata3 disruption in mouse embryos, in situ hybridization and immunostaining for BMP4 and FGF8 |
Development |
Medium |
34383890
|
| 2022 |
Loss of GATA3 function in p18-deficient background in mice directly induces basal-like mammary tumors. Haploid loss of Gata3 impairs luminal differentiation, promotes basal differentiation, and p18 is identified as a downstream target of GATA3 that restrains mammary epithelial cell proliferation. |
Genetically engineered mouse models (Gata3/p18 double mutants), mammary gland phenotyping, immunostaining, flow cytometry |
Theranostics |
High |
34976209
|
| 2019 |
ISL1 physically interacts with GATA3, and genome-wide mapping shows substantial co-occupancy of ISL1 and GATA3 binding regions in neuroblastoma cells; together they synergistically regulate oncogenic pathways including LMO1 and LIN28B. |
Co-IP of ISL1-GATA3, ISL1 ChIP-seq, RNA-seq, neuroblastoma cell KD functional assays |
Theranostics |
Medium |
30867811
|
| 2021 |
A Gata3 enhancer (Gata3 +674/762) controls ILC2 differentiation and high-level GATA3 expression specifically in ILC2s, while playing only a minimal role in Th2 cell differentiation, demonstrating distinct regulatory mechanisms for the same GATA3-driven type 2 effector program in innate vs. adaptive lymphocytes. |
CRISPR deletion of Gata3 enhancer in mice, ILC2 and Th2 development analysis, type 2 inflammatory response assays |
PNAS |
High |
34353913
|
| 2024 |
ILC2-specific Gata3-related tandem super-enhancers (G3SE) induce high GATA3 expression in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency with minimal impact on other ILC lineages or Th2 cells. Cnot6l (part of the CCR4-NOT deadenylase complex) is identified as a possible GATA3 target during ILC2 development. |
CRISPR deletion of G3SE in mice, single-cell RNA-seq, flow cytometry, developmental stage analysis |
Nature Communications |
High |
38969652
|
| 2024 |
A distal enhancer region (mG900, ~926-970 kb downstream of GATA3) interacts with the GATA3 transcription start site in Th2 cells and is required for GATA3 expression and Th2 differentiation during house dust mite-induced allergic airway inflammation, but not during papain-induced inflammation. |
CRISPR deletion of mG900 region in mice, 4C-seq chromatin conformation analysis, ChIP-qPCR, allergic airway inflammation models |
PNAS |
High |
38923989
|
| 2014 |
GATA3 loss in bladder cancer cells (siRNA knockdown) promotes cell migration and invasion, associated with increased VEGF, MMP-2, MMP-9 expression/activity, increased N-cadherin, and decreased β-catenin; enforced GATA3 expression in UMUC3 cells inhibits migration and invasion. |
siRNA knockdown, enforced expression, migration/invasion assays, MMP activity assays, Western blot for EMT markers |
Cancer Biology & Therapy |
Medium |
24448324
|
| 2023 |
In hepatocytes, Gata3 regulates hepatic vascular reconstitution after hepatectomy by controlling expression of PEDF and VEGFA. Downregulation of Gata3 promotes liver sinusoidal endothelial cell proliferation and hepatic revascularization; overexpression of Gata3 leads to higher mortality in ALPPS mice, reversible by PEDF-neutralizing antibody. |
AAV-CRISPR screening in Alb-Cre mice with partial hepatectomy, patient-derived hepatic organoids with Gata3 inhibitor, ALPPS mouse model |
Journal of Hepatology |
Medium |
37918568
|
| 2022 |
GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. GATA3 deficiency combined with MDM2 inhibition significantly impairs tumor growth. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. |
GATA3 depletion combined with MDM2 inhibitors in vitro, in vivo, and patient-derived organoids/xenografts; p53 requirement established by genetic manipulation; pathway analysis |
Communications Biology |
High |
35440675
|