Affinage

GATA5

Transcription factor GATA-5 · UniProt Q9BWX5

Length
397 aa
Mass
41.3 kDa
Annotated
2026-04-28
73 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GATA5 is a zinc-finger transcription factor that directs specification and differentiation of cardiac, endodermal, and endothelial cell lineages by binding GATA elements on target promoters and cooperating with lineage-specific co-regulators. It activates cardiac promoters (ANF, β-MHC, cTnC) through physical interaction with the coactivator p300 and functional synergy with NF-ATc, while in the intestine it partners with HNF-1α via its C-terminal zinc finger to co-activate genes such as lactase-phlorizin hydrolase and Fabpl (PMID:10567378, PMID:12011060, PMID:12163407). GATA5 operates downstream of Nodal/BMP signaling and upstream of Nkx2.5 and Notch pathway components during heart development, and its transcriptional activity requires SUMOylation at K360; loss of Gata5 in mice causes bicuspid aortic valve through defective endocardial differentiation, while compound Gata4/Gata5 or Gata5/Gata6 mutants reveal functional redundancy in cardiomyocyte specification and outflow tract morphogenesis (PMID:10580005, PMID:21633169, PMID:28285006, PMID:17950269). Epigenetic silencing of the GATA5 promoter by CpG hypermethylation, which disrupts USF1-mediated activation, contributes to transcriptional inactivation in colorectal and gastric cancers, where GATA5 re-expression restores downstream tumor-suppressive targets including trefoil factors, inhibin-α, and Dab2 (PMID:14612389, PMID:22625849).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Establishing GATA5 as a cardiac transcription factor: cloning of mouse GATA5 revealed it binds and transactivates the cardiac troponin C enhancer and showed dynamic expression from precardiac mesoderm through atrial endocardium, defining it as a cardiac-expressed GATA family member with transactivation capacity.

    Evidence cDNA isolation, transactivation assays in non-cardiac cell lines, in situ hybridization in mouse embryos

    PMID:9079664 PMID:9119112

    Open questions at the time
    • Endogenous target gene repertoire unknown
    • Functional requirement in vivo not yet tested
    • Relationship to other cardiac GATA factors unclear
  2. 1999 High

    Demonstrating in vivo necessity and sufficiency for heart development: zebrafish faust mutants lacking gata5 had reduced myocardial precursors and lost nkx2.5 expression, while gata5 overexpression induced ectopic beating tissue, establishing GATA5 as both necessary and sufficient for myocardial specification.

    Evidence Loss-of-function faust mutant and gain-of-function overexpression in zebrafish

    PMID:10580005

    Open questions at the time
    • Mechanism of Nkx2.5 activation (direct vs. indirect) not resolved
    • Mammalian in vivo requirement not yet tested
  3. 1999 High

    Identifying the p300 coactivator mechanism and defining GATA5's activation domain: GATA5 physically interacts with p300 to activate ANF transcription, and structure-function analysis mapped a C-terminal activation domain essential for cardiac promoter transactivation.

    Evidence Co-IP of GATA5–p300, E1A competition assay, deletion mutagenesis with reporter assays

    PMID:10212267 PMID:10501969 PMID:10567378

    Open questions at the time
    • Other coactivators or chromatin remodelers not explored
    • Whether p300 interaction is required in vivo not tested
  4. 2000 High

    Revealing a dual role in endoderm specification and an unexpected female genitourinary phenotype in mammals: Xenopus GATA5 potently induced endodermal markers and respecified mesoderm toward endoderm, while mouse Gata5 knockout unexpectedly produced genitourinary defects rather than overt cardiac malformations, exposing functional redundancy among mammalian GATA factors.

    Evidence Xenopus animal cap assays and microinjection; targeted Gata5 deletion in mice

    PMID:10866681 PMID:11003835

    Open questions at the time
    • Mechanism of genitourinary patterning by GATA5 uncharacterized
    • Redundancy with GATA4/GATA6 not formally tested in mammals yet
  5. 2001 High

    Placing GATA5 downstream of Nodal/BMP signaling in endoderm and heart specification: genetic epistasis showed gata5 acts downstream of Nodal signaling cooperating with Bon and requiring Cas for endoderm, and downstream of Bmp2b/Oep for myocardial nkx2.5 expression.

    Evidence Double-mutant epistasis, mRNA rescue of bmp2b and Zoep mutants in zebrafish

    PMID:11092818 PMID:11397003

    Open questions at the time
    • Direct transcriptional targets of GATA5 in endoderm specification not identified
    • Whether GATA5 is a direct BMP target not proven
  6. 2001 High

    Establishing GATA5 as a key intestinal transcriptional regulator through cooperation with HNF-1α: GATA5 synergistically activated intestinal gene promoters (LPH, SI) with HNF-1α, and this cooperation was later shown to require physical association via the C-terminal zinc finger of GATA5 and the HNF-1α homeodomain.

    Evidence Cotransfection in Caco-2 cells, Co-IP, domain mutagenesis, promoter mutation analysis

    PMID:11408257 PMID:12011060

    Open questions at the time
    • In vivo intestinal phenotype of Gata5 loss not characterized
    • Whether GATA5–HNF-1α interaction is regulated by signaling unknown
  7. 2002 High

    Defining GATA5's role in endocardial differentiation and functional synergy with NF-ATc: GATA5 was induced early in endothelial-to-endocardial differentiation; its inhibition blocked terminal endocardial differentiation, and GATA5/NF-ATc synergy activated endocardial transcription.

    Evidence In vitro cardiogenic differentiation model, antisense inhibition, NF-ATc inhibition, reporter assay

    PMID:12163407

    Open questions at the time
    • Direct NF-ATc physical interaction with GATA5 not demonstrated
    • In vivo endocardial-specific requirement not yet tested
  8. 2003 High

    Revealing GATA5 as an epigenetically silenced tumor suppressor: CpG hypermethylation of the GATA5 promoter silences it in colorectal and gastric cancers; demethylation or exogenous GATA5 restores expression of downstream tumor-suppressive targets (trefoil factors, inhibin-α, Dab2).

    Evidence Methylation-specific PCR, demethylation treatment, exogenous GATA5 expression with target gene readout

    PMID:14612389

    Open questions at the time
    • Whether GATA5 directly binds these downstream promoters not shown by ChIP
    • In vivo tumor suppression not demonstrated
  9. 2007 High

    Establishing redundancy between GATA5 and GATA6 in cardiomyocyte specification and identifying the Gridlock interaction: double depletion of gata5/gata6 abolished cardiomyocyte specification entirely, while Gridlock (Grl) was identified as a physical partner that represses GATA5-mediated transcription to modulate cardiomyocyte proliferative growth.

    Evidence Double morpholino knockdown with mRNA rescue in zebrafish; Co-IP of Grl–Gata5 complex and reporter assay

    PMID:17715064 PMID:17950269

    Open questions at the time
    • Structural basis of Grl–Gata5 interaction unknown
    • Whether Grl–Gata5 interaction is conserved in mammals not tested
  10. 2009 High

    Demonstrating Gata4/Gata5 genetic interaction for mammalian cardiac development: compound Gata4+/−;Gata5−/− mouse mutants died at mid-gestation with cardiomyocyte proliferation defects, formally proving mammalian functional redundancy between GATA4 and GATA5 in heart development.

    Evidence Compound knockout mouse genetics, cardiomyocyte proliferation assays, histology

    PMID:19889636

    Open questions at the time
    • Shared versus unique transcriptional targets of GATA4 and GATA5 not delineated
    • Whether compound heterozygosity is relevant in human disease unknown
  11. 2011 High

    Identifying GATA5 as a cause of bicuspid aortic valve and linking it to the Notch pathway: endocardial-specific Gata5 deletion in mice recapitulated BAV through defective endocardial differentiation with deregulation of Notch pathway components; compound Gata4/Gata5 and Gata5/Gata6 mutants developed outflow tract defects.

    Evidence Global and endocardial-specific Cre-mediated Gata5 knockout, Notch pathway gene expression analysis, compound mutant analysis

    PMID:21633169 PMID:21839733

    Open questions at the time
    • Whether GATA5 directly regulates Notch ligand/receptor promoters not confirmed by ChIP
    • Human genetic validation of GATA5 mutations causing BAV limited
  12. 2011 High

    Revealing Gata5 as part of a self-reinforcing endoderm specification kernel with Otx2 and Gata6: Otx2 directly binds and activates the gata5 promoter, and Gata5/Gata6 positively cross-regulate each other to lock on endoderm fate; Smarcd3b cooperates with Gata5 to cell-autonomously induce cardiac progenitor fate.

    Evidence ChIP for Otx2 at gata5 locus, promoter reporter assays, transplantation experiments in zebrafish

    PMID:21715426 PMID:21756893

    Open questions at the time
    • Whether the Otx2–Gata5 regulatory circuit is conserved in mammals unknown
    • Chromatin remodeling mechanism of Smarcd3b–Gata5 cooperation not characterized
  13. 2012 High

    Identifying USF1 as a direct upstream activator of GATA5 transcription whose binding is blocked by CpG methylation: USF1 binds an E-box in the GATA5 promoter; methylation of this site diminishes USF1 binding, providing a molecular link between promoter methylation and GATA5 silencing.

    Evidence EMSA, ChIP, site-directed mutagenesis, endogenous GATA5 expression upon USF1 overexpression

    PMID:22625849

    Open questions at the time
    • Whether USF1 loss phenocopies GATA5 silencing in cancer not tested
    • Other transcription factors regulating GATA5 promoter not systematically identified
  14. 2017 High

    Demonstrating that SUMOylation at K360 is essential for GATA5 transcriptional activity in cardiac development: K360R mutation abolished GATA5's ability to rescue cardiac differentiation in morphants, and a SUMO-fused GATA5 rescued heart defects in ubc9 mutants, establishing post-translational modification as a key regulatory mechanism.

    Evidence Western blot, K-to-R mutagenesis, mRNA rescue in gata5 morphant and ubc9 mutant zebrafish

    PMID:28285006

    Open questions at the time
    • SUMO E3 ligase responsible for GATA5 SUMOylation not identified
    • Whether SUMOylation regulates protein–protein interactions of GATA5 unknown
    • Mammalian relevance of GATA5 SUMOylation not tested
  15. 2019 High

    Placing GATA5 in the SIRT6/Nkx3.2 epigenetic pathway controlling blood pressure: endothelial SIRT6 deacetylates H3K9 to repress Nkx3.2, thereby upregulating GATA5; endothelial-specific SIRT6 deletion reduces GATA5 and exacerbates hypertension.

    Evidence Endothelial-specific SIRT6 knockout mice, H3K9 deacetylation assay, gene expression analysis

    PMID:30894089

    Open questions at the time
    • How GATA5 mechanistically regulates blood pressure at the vascular level unknown
    • Direct targets of GATA5 in endothelial cells mediating blood pressure regulation not identified
  16. 2022 Medium

    Expanding GATA5's direct target repertoire: ChIP confirmed GATA5 binds the ARHGAP9 promoter to suppress lung adenocarcinoma growth, and GATA5 physically associates with cathepsin S to promote angiogenesis via Angpt2/Flk1 and MMP2/MMP9 upregulation.

    Evidence ChIP and luciferase reporter for ARHGAP9; Co-IP of GATA5–cathepsin S, ischemic hindlimb model with endothelial GATA5 overexpression

    PMID:35040754 PMID:35429678

    Open questions at the time
    • GATA5–cathepsin S interaction not validated by reciprocal pulldown or domain mapping
    • Whether ARHGAP9 is a general or context-specific GATA5 target unknown
    • Genome-wide ChIP-seq for GATA5 in any tissue still lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: genome-wide identification of direct GATA5 targets by ChIP-seq in cardiac, endothelial, and intestinal contexts; the structural basis for GATA5's selectivity among GATA motifs and its interaction surfaces with diverse partners; the full spectrum of post-translational modifications regulating GATA5 activity; and the precise mechanism by which GATA5 suppresses Wnt/β-catenin signaling in cancer.
  • No genome-wide binding profile (ChIP-seq) available for GATA5
  • No crystal or cryo-EM structure of GATA5 or its complexes
  • Mechanism of cytoplasmic β-catenin sequestration by GATA5 not biochemically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 12 R-HSA-74160 Gene expression (Transcription) 9 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 3
Partners
EP300GATA4GATA6HEY2HNF1ANFATC1SMARCD3USF1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Zebrafish Gata5 (encoded by the faust locus) is required for the production of normal numbers of myocardial precursors, expression of nkx2.5, migration of cardiac primordia to the midline, ventricular tissue elaboration, and endodermal morphogenesis; overexpression of gata5 induces ectopic nkx2.5 expression and ectopic beating myocardial tissue. Loss-of-function (faust mutant analysis) and gain-of-function (gata5 overexpression) in zebrafish; in situ hybridization for myocardial gene expression Genes & development High 10580005
1997 Mouse GATA-5 binds to the CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C (cTnC) transcriptional enhancer and transactivates the cTnC enhancer in noncardiac muscle cell lines; it is expressed in precardiac mesoderm, atrial/ventricular chambers (E9.5), later restricted to atrial endocardium (E12.5), pulmonary mesenchyme, and subsets of smooth muscle cells. cDNA isolation, transactivation assays in non-cardiac cell lines, in situ hybridization/Northern blot for spatial/temporal expression Developmental biology High 9119112
1999 p300 acts as a coactivator of GATA-5 in cardiac-restricted transcription of the atrial natriuretic factor (ANF) gene; GATA-5 physically interacts with the C-terminal cysteine/histidine-rich domain of p300, and E1A represses GATA-5-dependent transcription by disrupting this interaction. Co-immunoprecipitation (Co-IP), dominant-negative p300 fragment assay, E1A repression assay, transactivation/luciferase reporter assay in cardiac cells The Journal of biological chemistry High 10567378
1999 GATA-5 has preferential binding affinity for a subset of GATA elements on cardiac promoters and differentially activates cardiac gene transcription; an activation domain in the carboxy-terminal region of GATA-5 is essential for transcriptional regulation of target promoters. Recombinant protein binding assays, structure-function analysis with deletion mutants, transactivation assays Mammalian genome High 10501969
1999 Among cardiac GATA factors, GATA-5 is the sole and potent transactivator of the beta-myosin heavy chain promoter; this transactivation depends on sequence-specific binding to the GATA element in the beta-MHC promoter, and leukemia inhibitory factor (LIF/gp130 signaling) increases GATA-5 transcripts and nuclear GATA-binding activity at this element. Promoter mutagenesis (GATA motif), transactivation assay, EMSA, LIF stimulation of cardiac myocytes The Journal of biological chemistry High 10212267
2001 Zebrafish Gata5 is required for endodermal cell generation at late blastula stages and maintenance of sox17 expression; Gata5 functions downstream of Nodal signaling, cooperates with the Mix-type transcription factor Bon, and requires cas function for endoderm formation; dominant genetic interactions among fau/gata5, bon, and cas confirm they operate in the same pathway. Mutant analysis, overexpression rescue, epistasis genetics (double mutants and suppressor analysis), in situ hybridization Development (Cambridge, England) High 11092818
2001 Bmp2b and Oep regulate gata5 expression in zebrafish myocardial precursors; forced expression of gata5 in bmp2b or Zoep mutants restores nkx2.5 and myocardial sarcomeric gene expression, placing Gata5 downstream of Bmp2b and Oep in the pathway regulating nkx2.5 and early myocardial differentiation. Zebrafish mutant analysis, gata5 mRNA overexpression rescue, in situ hybridization for nkx2.5 and cmlc1 Developmental biology High 11397003
2000 GATA5 is expressed in vegetal/endodermal cells of Xenopus from early gastrula stage; GATA4 and GATA5 are potent inducers of endodermal marker genes in animal cap assays, while other GATA factors are weak; GATA5 injection into the dorsal marginal zone respecifies mesoderm toward endoderm, disrupting convergence and extension; GATA5 is induced by high-dose activin in an FGF-independent manner, positioning endodermal induction in TGF-beta/FGF signaling context. Xenopus animal cap assays, microinjection/fate respecification, activin induction assay Development (Cambridge, England) High 11003835
2000 Targeted deletion of mouse GATA5 results in female genitourinary abnormalities (vaginal, uterine defects, hypospadias) without cardiac or other defects, demonstrating a specific in vivo role for GATA5 in female genitourinary system development. Gene targeting (null allele), homozygous knockout mouse analysis Molecular and cellular biology High 10866681
2001 GATA-5 and HNF-1alpha synergistically activate the lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) promoters; GATA-5 cooperates functionally with HNF-1alpha and is necessary for maximal activation of intestinal gene promoters. Cotransfection/transactivation assay in Caco-2 cells, promoter deletion/mutation analysis American journal of physiology. Gastrointestinal and liver physiology Medium 11408257
2002 GATA-5 and HNF-1alpha physically associate both in vivo and in vitro; this interaction is mediated by the C-terminal zinc finger of GATA factors and the homeodomain of HNF-1alpha; physical association is required for cooperative activation of the lactase-phlorizin hydrolase promoter; HNF-1alpha activation domains and DNA-binding sites are essential for cooperativity. Co-IP (in vivo), in vitro pulldown, deletion mutagenesis of both proteins, transactivation assay with promoter mutants The Journal of biological chemistry High 12011060
2002 GATA5 is induced at an early stage of endothelial-endocardial differentiation prior to Tie2 and ErbB3; inhibition of GATA5 expression or NF-ATc activation blocks terminal endocardial differentiation at a pre-endocardial stage; GATA5 and NF-ATc synergistically activate endocardial transcription. In vitro cardiogenic differentiation model, antisense inhibition of GATA5, NF-ATc inhibition, luciferase reporter (synergy assay) Development (Cambridge, England) High 12163407
2002 GATA-5 functionally interacts with Sp1 and Sp3 to regulate the rat NHE3 promoter; GATA-5 bound to a GATA box in exon 1 acts synergistically with Sp1/Sp3 at three upstream Sp-binding sites. Transient transfection (Caco-2, IEC-6, SL2 cells), deletion/mutation analysis, EMSA, forced Sp1/Sp3 expression in SL2 cells The Journal of biological chemistry Medium 12464626
2003 GATA-5 promoter is hypermethylated and transcriptionally silenced in colorectal and gastric cancers; demethylation restores GATA-5 expression and the expression of downstream target genes (trefoil factors, inhibin-alpha, Dab2); exogenous GATA-5 overrides methylation at downstream promoters to activate target genes. Methylation-specific PCR, demethylation (drug and genetic), exogenous GATA-5 expression with target gene reporter assays Molecular and cellular biology High 14612389
2004 GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein (Fabpl) gene promoter in cooperation with HNF-1alpha; GATA factors bind HNF-1alpha in solution; GATA-4 and GATA-5 (but not GATA-6) activate the proximal Fabpl GATA site; cooperative activation requires intact GATA and HNF-1 binding sites. Cell transfection, co-immunoprecipitation (binding in solution), promoter mutation analysis, in vivo mouse mosaic Gata4 inactivation American journal of physiology. Gastrointestinal and liver physiology Medium 14715527
2007 In zebrafish, gata5 and gata6 are functionally redundant for specification of cardiomyocytes; embryos depleted of both are heartless, while depletion of any single factor causes only morphogenetic defects; restoring either gata5 or gata6 alone rescues cardiomyocyte specification. Morpholino knockdown (single and double), mRNA rescue in zebrafish Developmental biology High 17950269
2007 Gridlock (Grl), a bHLH transcription factor, forms a protein complex with Gata5 through its carboxyl region and represses Gata5-mediated transcription via its bHLH domain; Gata5 (but not Gata4) counterbalances Grl's negative regulation of cardiomyocyte proliferative growth in zebrafish. Biochemical co-immunoprecipitation (complex formation), luciferase reporter assay (repression of Gata5 activity), in vivo zebrafish genetics (grl mutations and Grl overexpression) Proceedings of the National Academy of Sciences of the United States of America High 17715064
2008 In Xenopus, GATA5 is essential for early development of heart and liver precursors and acts upstream of GATA4; one early direct target of GATA5 is the homeobox gene Hex. Morpholino knockdown in Xenopus, epistasis analysis with GATA4/GATA6, target gene (Hex) identification BMC developmental biology Medium 18662378
2009 Gata4 and Gata5 cooperatively regulate cardiac myocyte proliferation in mice; Gata4+/-Gata5-/- compound mutants die at mid-gestation with cardiovascular defects including cardiomyocyte proliferation defects and cardiac chamber maturation abnormalities, demonstrating functional redundancy between the two factors. Compound mouse knockout (Gata5 null allele lacking exons 2-3 encoding zinc finger domains), histology, cardiomyocyte proliferation assays The Journal of biological chemistry High 19889636
2011 Targeted deletion of Gata5 in mice leads to bicuspid aortic valve (BAV) formation; endocardial cell-specific inactivation of Gata5 recapitulates BAV; Gata5 loss does not alter endocardial cell proliferation or cushion formation but causes defective endocardial cell differentiation through deregulation of Notch pathway components and other endocardial regulators. Global and endocardial-specific Cre-mediated Gata5 knockout mice, histological and molecular analysis of valve morphology, Notch pathway gene expression analysis The Journal of clinical investigation High 21633169
2011 Compound Gata4/Gata5 and Gata5/Gata6 mouse mutants develop severe outflow tract defects (DORV, VSD); expression of Tbx20, Mef2c, Hey1, and Hand2 is reduced, indicating that GATA5 interacts genetically with GATA4 and GATA6 in endocardial cushion formation and outflow tract morphogenesis. Compound heterozygous mouse genetics, cardiac morphology assessment, transcription factor expression analysis Developmental biology High 21839733
2011 Smarcd3b and Gata5 together promote a cardiac progenitor cell (CPC) fate in zebrafish; overexpression induces enlarged hearts; cells overexpressing both migrate to the heart and differentiate as cardiomyocytes, endocardium, and smooth muscle cell-autonomously, even in host embryos lacking endoderm or cardiac mesoderm. Zebrafish overexpression, morpholino knockdown, transplantation experiments (cell autonomy), in situ hybridization Development (Cambridge, England) High 21715426
2011 An evolutionarily conserved endoderm specification kernel in zebrafish involves positive regulation between gata5 and gata6; otx2 directly activates gata5 and gata6 (ChIP confirmed); gata5 and gata6 in turn regulate each other positively to lock on mesendoderm specification; functional assays identify a basal promoter of gata5 driven by Otx2 and Gata5/6. Morpholino knockdowns, qRT-PCR, in situ hybridization, mRNA rescue, chromatin immunoprecipitation (ChIP), promoter reporter assays Developmental biology High 21756893
2012 USF1 activates GATA5 transcription by binding to an E-box motif (5'-CACGTG-3') at bp -118 to -113 in the mouse GATA5 promoter; CpG methylation of this E-box diminishes USF1 binding; USF1 overexpression increases endogenous GATA5 expression. Site-directed mutagenesis, EMSA, affinity chromatography, ChIP (in vivo interaction), luciferase reporter assay, RT-PCR of endogenous GATA5 The Biochemical journal High 22625849
2017 GATA5 is SUMOylated at lysine residues K324 and K360; SUMOylation does not affect subcellular localization but is required for transcriptional activity; K360R mutation drastically reduces GATA5's ability to rescue cardiac precursor differentiation in gata5 morphants; a sumo-gata5 fusion but not wild-type gata5 rescues abnormal cardiac development in SUMOylation-deficient ubc9 mutants. Western blot for SUMOylation, immunostaining (subcellular localization), luciferase reporter assay (transcriptional activity), mRNA rescue in gata5 morphant and ubc9 mutant zebrafish, in situ hybridization Biochimica et biophysica acta. General subjects High 28285006
2019 SIRT6 induces GATA5 expression in endothelial cells by deacetylating histone H3K9, thereby inhibiting Nkx3.2 transcription; endothelial-specific SIRT6 deletion reduces GATA5 expression and exacerbates hypertension and cardiorenal injury; GATA5 is identified as a novel regulator of blood pressure downstream of SIRT6/Nkx3.2. Endothelial-specific SIRT6 knockout mice, H3K9 deacetylation assay, SIRT6 overexpression in vivo, gene expression analysis Circulation research High 30894089
2014 Gata5 deficiency in mice causes native airway constrictor hyperresponsiveness (AHR); Gata5-null lungs show reduced apolipoprotein E (apoE) and increased IL-13 mRNA expression, indicating that Gata5 regulates apoE and IL-13 in vivo. Gata5-/- and Gata5+/- mouse models, invasive airway constrictor responsiveness measurement, gene expression profiling (microarray + qRT-PCR), immunostaining American journal of respiratory cell and molecular biology High 24199649
2018 GATA5 suppresses cholangiocarcinoma (CCA) cell growth and metastasis via the Wnt/β-catenin pathway; specific β-catenin inhibitor or β-catenin siRNA abolishes the difference in proliferation/metastasis between GATA5-overexpressing and control CCA cells. GATA5 overexpression in CCA cell lines, β-catenin inhibitor (salinomycin) and siRNA rescue experiments, proliferation and invasion assays Translational oncology Medium 29547757
2019 GATA5 co-localizes with β-catenin in the cytoplasm of HCC cells, preventing β-catenin nuclear entry; GATA5 overexpression decreases β-catenin and reprogramming genes (p-Oct4, Nanog, Klf4, c-myc, EpCAM), inhibiting HCC cell malignant behaviors. Co-localization by confocal microscopy, GATA5 overexpression and siRNA knockdown, Western blotting, cell proliferation/invasion/migration assays Journal of cellular and molecular medicine Medium 30672133
2009 Alternative GATA5 transcript from an alternate promoter within intron 1 produces a short isoform lacking exon 1 (aa 226-404, single zinc finger) that localizes to the nucleus and retains ability to transactivate the ANF promoter but less efficiently than full-length GATA5. cDNA/genomic cloning, promoter reporter assay, transgenic mouse reporter, transfection and transactivation assay American journal of physiology. Gastrointestinal and liver physiology Medium 19779014
1997 Chicken GATA-5 is expressed from alternative first exons producing two distinct isoforms; the minor isoform with a single zinc finger localizes to the nucleus and can bind a GATA site but is compromised in transactivation of a target gene compared to the major dual-zinc-finger isoform. cDNA/genomic cloning, nuclear localization assay (transfection), gel-shift (DNA-binding), transactivation reporter assay The Journal of biological chemistry Medium 9079664
2006 GATA5 binds the GATA site adjacent to the +331G/A polymorphism in the progesterone receptor (hPR) promoter, activates the hPR-luciferase reporter in breast cancer cells, increases endogenous hPR transcript, preferentially activates the PR-B isoform promoter, and more strongly activates the +331A variant than the +331G variant. Transactivation/luciferase reporter assay, endogenous gene expression analysis (qRT-PCR), comparison of +331G vs +331A promoter constructs Cancer research Medium 16452193
2022 GATA5 directly binds the ARHGAP9 promoter and activates its transcription in lung adenocarcinoma cells; GATA5-induced ARHGAP9 upregulation inhibits lung adenocarcinoma cell proliferation, invasion, and migration; GATA5 silencing reverses the inhibitory effect of ARHGAP9. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), Western blot, CCK-8, EdU staining, transwell, colony formation assays Bioengineered Medium 35040754
2022 Endothelial GATA5 promotes angiogenesis by inducing cathepsin S (Cat S) expression; GATA5 physically binds Cat S (immunoprecipitation); Cat S mediates GATA5-dependent upregulation of Angpt2/Flk1 and MMP2/MMP9, promoting endothelial tube formation and migration. Ischemic hindlimb model with endothelial GATA5 overexpression (EC-Ad mice), Co-IP (GATA5–Cat S interaction), siRNA knockdown, tube formation and migration assays in HUVECs Biochemical and biophysical research communications Medium 35429678
2017 Compound heterozygous GATA5 mutations (p.Ser19Trp and p.Arg202Gln) fail to rescue cardia bifida in zebrafish, mislocalize to subnuclear foci in HEK293 cells, and exhibit reduced transcriptional activity, demonstrating that both mutations are loss-of-function and that normal GATA5 nuclear localization is required for function. Zebrafish rescue assay (cardia bifida morphant), subcellular localization (immunofluorescence in HEK293), luciferase reporter (transcriptional activity) Human genetics Medium 28180938
2025 GATA5 and ISL1 co-regulate the Wnt signaling pathway to promote transformation of fibroblasts into functional cardiomyocytes post-myocardial infarction; adenoviral overexpression of GATA5 and ISL1 in MI mice ameliorates cardiac function and attenuates myocardial fibrosis. Single-cell RNA-seq and scATAC-seq of MI mouse hearts, adenoviral GATA5/ISL1 overexpression in vivo, RNA sequencing of overexpressing human cardiac fibroblasts, proteomic analysis Cardiovascular research Medium 40460294

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Gata5 is required for the development of the heart and endoderm in zebrafish. Genes & development 346 10580005
2003 GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Molecular and cellular biology 214 14612389
1997 GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. Developmental biology 210 9119112
2009 GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 164 19509152
2001 Multiple roles for Gata5 in zebrafish endoderm formation. Development (Cambridge, England) 147 11092818
2011 Loss of Gata5 in mice leads to bicuspid aortic valve. The Journal of clinical investigation 137 21633169
2019 Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury Through Targeting Nkx3.2-GATA5 Signaling. Circulation research 133 30894089
2012 Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease. Journal of molecular and cellular cardiology 112 22641149
2013 Cross-repressive interactions between SOC1 and the GATAs GNC and GNL/CGA1 in the control of greening, cold tolerance, and flowering time in Arabidopsis. Plant physiology 110 23739688
2000 A role for GATA5 in Xenopus endoderm specification. Development (Cambridge, England) 105 11003835
2001 Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha. American journal of physiology. Gastrointestinal and liver physiology 99 11408257
2000 Abnormalities of the genitourinary tract in female mice lacking GATA5. Molecular and cellular biology 99 10866681
2011 GATA5 interacts with GATA4 and GATA6 in outflow tract development. Developmental biology 87 21839733
2013 Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve. BMC medical genetics 83 23578328
2014 GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. International journal of molecular medicine 80 24638895
2002 Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells. Development (Cambridge, England) 78 12163407
1999 p300 protein as a coactivator of GATA-5 in the transcription of cardiac-restricted atrial natriuretic factor gene. The Journal of biological chemistry 77 10567378
2009 Gata4 and Gata5 cooperatively regulate cardiac myocyte proliferation in mice. The Journal of biological chemistry 76 19889636
2001 Bmp2b and Oep promote early myocardial differentiation through their regulation of gata5. Developmental biology 71 11397003
2002 Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter. The Journal of biological chemistry 69 12011060
2004 GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene in concert with HNF-1alpha. American journal of physiology. Gastrointestinal and liver physiology 66 14715527
2007 Gata5 and Gata6 are functionally redundant in zebrafish for specification of cardiomyocytes. Developmental biology 63 17950269
2015 Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas. World journal of gastroenterology 56 25759530
2002 Transcriptional regulation of the rat NHE3 gene. Functional interactions between GATA-5 and Sp family transcription factors. The Journal of biological chemistry 48 12464626
2012 GATA5 loss-of-function mutations underlie tetralogy of fallot. International journal of medical sciences 46 23289003
2009 Anthocyanins from black soybean seed coats preferentially inhibit TNF-alpha-mediated induction of VCAM-1 over ICAM-1 through the regulation of GATAs and IRF-1. Journal of agricultural and food chemistry 46 19627149
2012 A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. International journal of molecular medicine 45 23175127
2008 GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos. BMC developmental biology 45 18662378
2010 Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World journal of gastroenterology 44 20222162
2011 Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. Development (Cambridge, England) 42 21715426
2012 GATA5 loss-of-function mutation responsible for the congenital ventriculoseptal defect. Pediatric cardiology 41 22961344
1999 Functional analysis and chromosomal mapping of Gata5, a gene encoding a zinc finger DNA-binding protein. Mammalian genome : official journal of the International Mammalian Genome Society 33 10501969
2014 GATA5 loss-of-function mutation in familial dilated cardiomyopathy. International journal of molecular medicine 32 25543888
2006 GATA5 activation of the progesterone receptor gene promoter in breast cancer cells is influenced by the +331G/A polymorphism. Cancer research 32 16452193
1997 Transcripts for functionally distinct isoforms of chicken GATA-5 are differentially expressed from alternative first exons. The Journal of biological chemistry 31 9079664
1999 GATA-5 is involved in leukemia inhibitory factor-responsive transcription of the beta-myosin heavy chain gene in cardiac myocytes. The Journal of biological chemistry 30 10212267
2012 GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU international 28 22289415
2016 WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report. Cellular oncology (Dordrecht, Netherlands) 27 27491556
2007 Evaluation of GATA-4 and GATA-5 methylation profiles in human pancreatic cancers indicate promoter methylation patterns distinct from other human tumor types. Cancer biology & therapy 27 17912029
2015 GATA5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient. Molecular genetics & genomic medicine 26 27066509
2014 Somatic GATA5 mutations in sporadic tetralogy of Fallot. International journal of molecular medicine 26 24573614
2012 Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation. Clinics (Sao Paulo, Brazil) 24 23295592
2016 Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma. Clinical chemistry and laboratory medicine 23 27171388
2014 Promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in invasive ductal breast carcinoma. Molecular and cellular biochemistry 20 25148870
2007 Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5. Proceedings of the National Academy of Sciences of the United States of America 18 17715064
2018 Methylation-Mediated Silencing of GATA5 Gene Suppresses Cholangiocarcinoma Cell Proliferation and Metastasis. Translational oncology 17 29547757
2014 GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma. Oncology reports 16 24549248
2011 An evolutionarily conserved kernel of gata5, gata6, otx2 and prdm1a operates in the formation of endoderm in zebrafish. Developmental biology 16 21756893
2022 Overexpression of GATA5 Inhibits Prostate Cancer Progression by Regulating PLAGL2 via the FAK/PI3K/AKT Pathway. Cancers 15 35565203
2019 GATA5 inhibits hepatocellular carcinoma cells malignant behaviours by blocking expression of reprogramming genes. Journal of cellular and molecular medicine 15 30672133
2012 Upstream stimulatory factor 1 activates GATA5 expression through an E-box motif. The Biochemical journal 15 22625849
2014 GATA5 and endothelial nitric oxide synthase expression in the ascending aorta is related to aortic size and valve morphology. The Annals of thoracic surgery 14 24766859
2023 Jagged/Notch proteins promote endothelial-mesenchymal transition-mediated pulmonary arterial hypertension via upregulation of the expression of GATAs. Journal of cellular and molecular medicine 13 36942326
2017 GATA5 SUMOylation is indispensable for zebrafish cardiac development. Biochimica et biophysica acta. General subjects 13 28285006
2017 Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies. Human genetics 11 28180938
2015 Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells. Oncology letters 11 26870297
2014 Gata5 deficiency causes airway constrictor hyperresponsiveness in mice. American journal of respiratory cell and molecular biology 11 24199649
2014 Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma. BMC cancer 10 24533449
2011 Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors. PloS one 10 22028801
2022 GATA binding protein 5 (GATA5) induces Rho GTPase activating protein 9 (ARHGAP9) to inhibit the malignant process of lung adenocarcinoma cells. Bioengineered 9 35040754
2022 Endothelial GATA5 positively regulates angiogenesis via cathepsin S-mediated Angpt2/Flk1 and MMP2/9 signaling pathways. Biochemical and biophysical research communications 9 35429678
2014 Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects. World journal of pediatrics : WJP 9 25515806
2022 Identification of non-synonymous variations in ROBO1 and GATA5 genes in a family with bicuspid aortic valve disease. Journal of human genetics 8 35534675
2018 Effect of Helicobacter pylori Infection on GATA-5 and TFF1 Regulation, Comparison Between Pediatric and Adult Patients. Digestive diseases and sciences 8 30083861
2009 Alternative promoter and GATA5 transcripts in mouse. American journal of physiology. Gastrointestinal and liver physiology 7 19779014
2021 Molecular genetic study on GATA5 gene promoter in acute myocardial infarction. PloS one 5 33684162
2025 Single-cell epigenomic and transcriptomic analysis unveils the pivotal role of GATA5/ISL1+ fibroblasts in cardiac repair post-myocardial infarction. Cardiovascular research 3 40460294
2021 NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block. Open life sciences 3 34901457
2025 Whole-Exome Sequencing Identifies Novel GATA5/6 Variants in Right-Sided Congenital Heart Defects. International journal of molecular sciences 2 40076735
2024 Coexistent HCN4 and GATA5 Rare Variants and Atrial Fibrillation in a Large Spanish Family. The Canadian journal of cardiology 1 38432398
2020 Overexpression of GATA5 Stimulates Paclitaxel to Inhibit Malignant Behaviors of Hepatocellular Carcinoma Cells. Cell journal 1 32779438
2025 Transcription factor GATA5 enhances autophagy by modulating miR-2765 in Penaeus vannamei under ammonia nitrogen stress. International journal of biological macromolecules 0 40553875
2025 N6-methyladenosine-modified ACSM3 mitigates lipid accumulation and suppresses tumor progression in ccRCC via GATA5/HMGCS2 axis and mTORC1 signaling. International journal of biological macromolecules 0 40992469