Affinage

GATA6

Transcription factor GATA-6 · UniProt Q92908

Length
595 aa
Mass
60.0 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GATA6 is a zinc-finger transcription factor and chromatin pioneer factor that directs lineage commitment and tissue identity across endoderm, heart, pancreas, lung, skin, and vascular systems by binding regulatory elements of fate-determining target genes (PMID:9832509, PMID:26109048, PMID:33054971). In the early embryo it is essential for primitive and visceral endoderm formation, acting upstream of HNF4 and within an FGF/ERK-driven tristable network where its levels, opposed by NANOG, dictate inner cell mass fate; ERK1/2 phosphorylation at S264 drives a positive-feedback autoactivation loop required for primitive endoderm commitment (PMID:9832509, PMID:24835466, PMID:25209243, PMID:29454706). Genome-wide, GATA6 co-binds enhancers with NANOG and then evicts epiblast factors, remodeling chromatin accessibility and enhancer-promoter contacts to activate extraembryonic-endoderm genes while repressing pluripotency genes, and it cooperates with EOMES/SMAD2/3 to license definitive endoderm (PMID:35871075, PMID:26109048, PMID:30629940). In organ development it acts combinatorially and dose-dependently with GATA4 in pancreatic specification and cardiovascular morphogenesis, repressing Hedgehog signaling through GATA sites in the Shh MACS1 enhancer and maintaining acinar and β-cell identity, with haploinsufficiency producing bicuspid aortic valve via MMP9 dysregulation and sinus node hypoplasia through loss of TBX3/EDN1 activation (PMID:23006325, PMID:23006330, PMID:26932670, PMID:24415953, PMID:29263149, PMID:29567669, PMID:33443158). It also governs lung alveolar type-1 differentiation and Wnt restriction, hair follicle and sebaceous duct lineage identity, and brown adipocyte development (PMID:11959831, PMID:18536717, PMID:28504705, PMID:37647897). GATA6 expression is itself tightly controlled epigenetically—supported by p300/EP300 acetylation and TET2-deposited 5hmC, and repressed by EZH2-mediated H3K27 methylation and HDAC1/2-STAT3-DNMT1-dependent promoter hypermethylation—a circuitry that toggles the classical-versus-basal subtype switch in pancreatic cancer, where GATA6 (with HNF1A/HNF4A) suppresses EGFR signaling, EMT, and tumor progression (PMID:32907838, PMID:35536676, PMID:33915173, PMID:33859766, PMID:33846140, PMID:25596178, PMID:27325420). In the broader cancer setting GATA6 acts as a context-dependent activator or repressor of targets including LGR5, REG4, VEGF-C, MUC1, and PKM2 (PMID:24452072, PMID:26387746, PMID:32103545, PMID:33060563, PMID:30834518). Heterozygous loss-of-function GATA6 mutations cause human pancreatic agenesis, explained by failure of definitive endoderm entry (PMID:30629940).

Mechanistic history

Synthesis pass · year-by-year structured walk · 38 steps
  1. 1998 High

    Established GATA6 as a master upstream regulator of visceral endoderm differentiation, placing it atop a transcriptional cascade where no endoderm-specifying factor had been genetically ordered.

    Evidence GATA6-null ES cells/mice, embryoid body differentiation, and HNF4 promoter activation assay

    PMID:9832509

    Open questions at the time
    • Did not define direct vs indirect target relationships genome-wide
    • Mechanism of GATA6 chromatin engagement not addressed
  2. 2001 High

    Showed GATA6 is a necessary mediator of cardiomyocyte hypertrophy, extending its role from development to adult cardiac stress responses.

    Evidence Adenoviral overexpression and dominant-negative GATA4-engrailed in cardiomyocytes plus transgenic mice

    PMID:11356841

    Open questions at the time
    • Direct hypertrophic target genes not delineated
    • Dominant-negative does not distinguish GATA6 from GATA4 function
  3. 2002 High

    Defined GATA6 as required for alveolar type-1 cell differentiation and direct activator of AT1-specific genes, expanding its lineage scope to distal lung.

    Evidence Dominant-negative GATA6-Engrailed transgenic mice and aquaporin-5 promoter trans-activation

    PMID:11959831

    Open questions at the time
    • Dominant-negative may affect other GATA factors
    • Endogenous GATA6 loss-of-function in lung not tested here
  4. 2006 Medium

    Identified GATA6 as required for pancreas specification and a physical Nkx2.2 partner, establishing tissue-specific protein interactions underlying its pancreatic role.

    Evidence Co-IP with Nkx2.2 and dominant-negative Gata6-Engrailed transgenic mice with histology

    PMID:16887115

    Open questions at the time
    • Co-IP not reciprocally validated for direct binding
    • Dominant-negative does not isolate endogenous GATA6 requirement
  5. 2006 High

    Revealed a GATA4/GATA6 dosage threshold for cardiovascular gene expression, demonstrating combinatorial and redundant function between the two factors.

    Evidence Compound heterozygous mouse genetics with histology and downstream marker analysis (MEF2C, beta-MHC)

    PMID:16847256

    Open questions at the time
    • Direct vs indirect regulation of MEF2C/beta-MHC not resolved
    • Cell-type specificity of dosage requirement not mapped
  6. 2008 High

    Connected GATA6 to Wnt signaling control in lung stem cell dynamics and to direct activation of canonical Wnt components in endoderm, defining a pathway-level node.

    Evidence Conditional lung Gata6-null mice with genetic rescue (Fzd2, beta-catenin); ChIP and reporter on Wnt6 promoter in F9 cells

    PMID:18536717 PMID:22607194

    Open questions at the time
    • Context-dependent canonical vs non-canonical Wnt switching mechanism unclear
    • F9 cell findings need in vivo validation
  7. 2009 Medium

    Linked GATA6 to nuclear envelope integrity and genome stability via emerin, an unexpected role beyond classical lineage transcription.

    Evidence siRNA knockdown in ovarian surface epithelial cells with emerin epistasis and nuclear morphology analysis

    PMID:19581290

    Open questions at the time
    • Direct transcriptional control of emerin by GATA6 not shown by binding data
    • Single cell-type, no in vivo confirmation
  8. 2012 High

    Demonstrated that combined GATA4/GATA6 loss causes pancreatic agenesis through progenitor proliferation and morphogenesis failure, defining the genetic basis for human GATA6-associated pancreatic agenesis.

    Evidence Conditional double-knockout mice with histology and progenitor marker analysis (two simultaneous publications)

    PMID:23006325 PMID:23006330

    Open questions at the time
    • Direct target genes driving proliferation defect not identified here
    • Relative GATA4 vs GATA6 contribution not separated
  9. 2013 Medium

    Showed endothelial GATA6 directly regulates vascular tone and inflammatory genes, extending its function to vascular homeostasis.

    Evidence Endothelial-specific Gata6 conditional KO mice with pulmonary artery pressure and target gene analysis

    PMID:23583651

    Open questions at the time
    • Direct binding to all named targets not all demonstrated
    • Single lab, mechanism of inflammatory recruitment incomplete
  10. 2014 High

    Quantitatively defined GATA6 as a dose-sensitive determinant of inner cell mass fate within a tristable NANOG/FGF/ERK network, resolving how PrE versus epiblast identity is set.

    Evidence Single-cell imaging and Gata6 dosage series with FGF/ERK manipulation; mathematical modeling

    PMID:24835466 PMID:25209243

    Open questions at the time
    • Direct molecular target of GATA6 enacting fate switch not isolated
    • Quantitative thresholds may be model-system specific
  11. 2014 High

    Identified GATA6 as a crucial regulator of Shh expression in the limb bud, repressing Shh/Gli1 with FOG co-factors and acting upstream of polydactyly phenotypes.

    Evidence Conditional Gata6 KO, forced expression, ChIP, reporter assay, and Shh/Gata6 genetic epistasis

    PMID:24415953

    Open questions at the time
    • Mechanism of FOG-dependent repression switch not detailed
    • How GATA6 chooses activation vs repression at different loci unclear
  12. 2014 Medium

    Defined GATA6 as a direct activator of LGR5 and REG4 in colorectal cancer, downregulated by miR-363, establishing a tumorigenicity axis.

    Evidence Overexpression/knockdown, luciferase reporter (miR-363/GATA6 3'UTR), and xenograft assays

    PMID:24452072 PMID:26387746

    Open questions at the time
    • Direct ChIP binding at LGR5/REG4 promoters not all confirmed in same study
    • Single lineage context
  13. 2014 Medium

    Showed GATA6/GATA4 maintain pancreatic endoderm identity by directly repressing Hedgehog through GATA sites in the Shh MACS1 enhancer.

    Evidence Double conditional KO and MACS1 enhancer reporter with GATA-site mutagenesis

    PMID:26932670

    Open questions at the time
    • Endogenous occupancy at MACS1 not shown by ChIP here
    • Single lab
  14. 2015 High

    Established GATA6 as a pioneer factor sufficient to reprogram cells to extraembryonic endoderm, acting as direct repressor of pluripotency genes and activator of endoderm genes.

    Evidence Inducible Gata6, reprogramming assays, ChIP-seq, and transcriptional profiling

    PMID:26109048

    Open questions at the time
    • Order of repression vs activation events not fully temporally resolved
    • Pioneer chromatin-opening mechanism characterized later
  15. 2015 High

    Defined GATA6 as a tumor suppressor in pancreatic cancer that directly represses EGFR and inflammatory pathways to maintain acinar identity.

    Evidence GEMMs with KrasG12V, ChIP-seq, RNA-seq, and human PDAC cell silencing

    PMID:25596178

    Open questions at the time
    • Mechanism of repression at EGFR pathway loci not detailed
    • Cofactors mediating repression not defined
  16. 2016 High

    Showed GATA6 inhibits EMT and dissemination in PDAC through direct and indirect transcriptional control of EMT genes, reinforcing its differentiation-maintaining role.

    Evidence Gain/loss-of-function in PDAC cells, ChIP-seq, RNA-seq, in vivo dissemination

    PMID:27325420

    Open questions at the time
    • Indirect EMT TF regulation not fully mapped
    • Patient-stratification implications not tested clinically
  17. 2016 Medium

    Identified gain-of-function GATA6 variants that enhance transcriptional activity and can drive atrial fibrillation, complementing loss-of-function disease mechanisms.

    Evidence Whole exome sequencing and reporter assays with GATA4/MEF2C co-expression

    PMID:27756709

    Open questions at the time
    • Reporter assay does not establish in vivo arrhythmogenic mechanism
    • Limited to three variants, single lab
  18. 2016 Medium

    Defined GATA6 control of hair follicle matrix progenitor renewal via Edaradd/NF-kB to protect proliferating cells from DNA damage, extending its role to epidermal stem cells.

    Evidence Conditional KO and keratinocyte rescue with Edaradd; DNA damage assays

    PMID:27908934

    Open questions at the time
    • Direct GATA6 binding at Edaradd not shown
    • Single lab
  19. 2017 High

    Established GATA6 as the lineage-identity determinant of the sebaceous duct and a driver of cellular dedifferentiation and self-renewal during wound healing.

    Evidence Conditional KO, lineage tracing, live imaging, clonogenic assays

    PMID:28504705

    Open questions at the time
    • Transcriptional targets enforcing SD identity not defined
    • Mechanism of dedifferentiation gain unclear
  20. 2017 High

    Defined GATA6 as required for adult β-cell insulin biosynthesis and secretion, acting through GATA-dependent Pdx1 expression.

    Evidence Pancreas-specific KO with glucose tolerance, insulin assays, EM, and GATA-site mutant reporter mice

    PMID:29263149

    Open questions at the time
    • Full β-cell target gene network not mapped
    • Direct vs indirect Pdx1 regulation partially resolved
  21. 2017 Medium

    Showed GATA6 cooperates with Sp1 and p300 to activate Aqp5 via histone acetylation, competing with HDAC3, illustrating its coactivator-recruitment mechanism.

    Evidence Co-IP (GATA6/Sp1/p300/HDAC3), ChIP for acetylation, and reporter assays

    PMID:28615712

    Open questions at the time
    • Co-IP interactions not reciprocally validated for direct contact
    • Single lab
  22. 2017 Medium

    Implicated GATA6 with NR5A1 in steroidogenesis in endometriotic cells, broadening its role to local estrogen production in disease.

    Evidence Ectopic expression and siRNA of GATA6/NR5A1 with estradiol output assays

    PMID:29402198

    Open questions at the time
    • Direct promoter binding at steroidogenic genes not shown
    • Single lab, in vitro only
  23. 2018 High

    Resolved how GATA6 sustains its own expression: ERK1/2 phosphorylation at S264 enables autoactivation, providing the post-translational switch for primitive endoderm commitment.

    Evidence Gata6-H2BGFP knock-in mouse, S264 site-directed mutagenesis, and promoter activation assay

    PMID:29454706

    Open questions at the time
    • Direct demonstration of ERK phosphorylation at S264 in vivo limited
    • Other phosphosites not surveyed
  24. 2018 High

    Defined the precise cellular requirement for GATA6 in bicuspid aortic valve via secondary-heart-field myocytes and MMP9-dependent valve remodeling, with human genetic validation.

    Evidence Haploinsufficient and cell-specific conditional KO mice, MMP9 analysis, human GWAS

    PMID:29567669

    Open questions at the time
    • Direct GATA6 regulation of MMP9 not shown by binding
    • Mechanism of ECM dysregulation incomplete
  25. 2019 High

    Showed GATA6 cooperates genome-wide with EOMES/SMAD2/3 to license definitive endoderm, mechanistically explaining human heterozygous GATA6 pancreatic agenesis.

    Evidence Isogenic and patient-derived hPSCs, directed differentiation, ChIP-seq of three factors, RNA-seq

    PMID:30629940

    Open questions at the time
    • Dosage threshold for human DE entry not precisely quantified
    • Cooperative complex assembly mechanism not structurally resolved
  26. 2019 Medium

    Expanded the GATA6 cancer target repertoire (CD137L, miR-520b/CREB1, PKM2) and showed context-dependent activator/repressor behavior across tumor types.

    Evidence ChIP, reporter assays, knockdown/overexpression, in vivo metastasis/tumorigenicity models

    PMID:30194255 PMID:30674866 PMID:30834518

    Open questions at the time
    • Cofactors determining activation vs repression at these loci unknown
    • Each target validated in single tumor context
  27. 2019 Medium

    Demonstrated GATA6 is itself repressed by GATA4 through proximal repressive sites, revealing cross-regulation between the two GATA factors in heart development.

    Evidence ChIP-qPCR, reporter assay, and Gata4 heterozygous mice

    PMID:31120883

    Open questions at the time
    • Mechanism of GATA4-mediated repression unclear
    • Single lab
  28. 2019 Medium

    Identified a GATA6-LOXL2 physical complex driving VEGFA-dependent angiogenesis, an example of non-transcription-factor partnership.

    Evidence Co-IP, RT-qPCR, ELISA, tube formation, xenograft in cholangiocarcinoma

    PMID:31322171

    Open questions at the time
    • Co-IP not reciprocally confirmed for direct binding
    • How LOXL2 modulates GATA6 activity unclear
  29. 2020 High

    Characterized GATA6 as a cardiac pioneer factor regulating SMYD1/HAND2/KDR for outflow tract formation, and showed a missense variant confers ectopic pioneer activity altering lineage output.

    Evidence Isogenic iPSC cardiomyocytes, RNA-seq, ATAC-seq, ChIP-seq comparing LoF and missense variants

    PMID:33054971

    Open questions at the time
    • Mechanism of ectopic pioneer activity of missense variant not fully defined
    • In vivo correlate of iPSC findings limited
  30. 2020 High

    Established that GATA6 expression is epigenetically silenced by EZH2 (H3K27me) to enforce the basal PDAC program, with GATA6 re-ablation confirming its functional importance.

    Evidence EZH2 ChIP-seq at GATA6 locus, RNA-seq, and epistatic GATA6 knockdown in EZH2-deficient cells

    PMID:32907838

    Open questions at the time
    • Trigger for EZH2 recruitment to GATA6 locus unknown
    • Reversibility window in patients untested
  31. 2020 Medium

    Identified additional context-dependent GATA6 repression targets (VEGF-C in bladder cancer, MUC1/beta-catenin axis in cholangiocarcinoma) and dose-sensitive lung-versus-liver fate control.

    Evidence ChIP, reporter mutagenesis, Co-IP, knockdown/overexpression, in vivo metastasis; hPSC lung differentiation

    PMID:29889101 PMID:32103545 PMID:33060563

    Open questions at the time
    • Switch between activator and repressor function not mechanistically explained
    • Each target in single tissue context
  32. 2021 High

    Defined a GATA6/HNF1A/HNF4A regulatory network controlling PDAC subtype identity, showing GATA6 loss is necessary but not sufficient for the basal switch.

    Evidence Dual-recombinase late-deletion mouse model, RNA-seq, human transcriptomics validation

    PMID:33846140

    Open questions at the time
    • Hierarchy among GATA6, HNF1A, HNF4A not fully ordered
    • Therapeutic exploitation not addressed
  33. 2021 Medium

    Showed epigenetic control of GATA6 levels in vascular and tumor contexts: HDAC1/2-STAT3-DNMT1 promoter hypermethylation represses it, while TET2-deposited 5hmC (SMAD4-supported) maintains it.

    Evidence MSP, ChIP, Co-IP, STAT3 K685 mutation, oxidative bisulfite sequencing, in vivo pharmacological rescue

    PMID:33859766 PMID:33915173

    Open questions at the time
    • Cross-talk between activating and repressive marks at GATA6 locus unresolved
    • Single lab per mechanism
  34. 2022 High

    Resolved the pioneer mechanism: GATA6 co-binds enhancers with NANOG then evicts epiblast factors and remodels chromatin and enhancer-promoter contacts to flip ICM cells to PrE fate.

    Evidence Inducible GATA6 ES cells and blastocysts, ChIP-seq, ATAC-seq, Hi-C/4C

    PMID:35871075

    Open questions at the time
    • Molecular trigger for epiblast-TF eviction not identified
    • Kinetics of chromatin remodeling at single-cell level limited
  35. 2022 High

    Identified EP300/p300 as a direct positive regulator of GATA6 expression whose loss drives the classical-to-basal PDAC switch and Wnt-inhibitor resistance.

    Evidence In vivo CRISPR screen, EP300 KO, GATA6 overexpression rescue, RNA-seq, chromatin accessibility

    PMID:35536676

    Open questions at the time
    • Whether EP300 acts directly at GATA6 locus vs broadly not fully resolved
    • Clinical reversal strategy untested
  36. 2021 High

    Established GATA6 as a direct activator of the sinus node program through TBX3 and EDN1, with haploinsufficiency causing hypoplastic sinus node and arrhythmia.

    Evidence Haploinsufficient and cell-specific KO mice, ECG, histology, chromatin binding and activation assays

    PMID:33443158

    Open questions at the time
    • Lineage-specific cofactors at TBX3/EDN1 not defined
    • Human relevance via genetics not tested here
  37. 2023 Medium

    Extended GATA6 roles to vascular inflammation/atherosclerosis (direct Cmpk2/Ccl5 targets via CMPK2-Nlrp3), brown adipocyte development, and vascular calcification (SIRT6-Nkx2.5-GATA6-ATM axis).

    Evidence Cell-specific KO, ChIP, AAV knockdown/rescue, lineage tracing, single-cell RNA-seq, Co-IP

    PMID:37339559 PMID:37647897 PMID:37914087

    Open questions at the time
    • Direct binding for all named targets not uniformly demonstrated
    • Each context single lab
  38. 2012 Medium

    Showed GATA6 with NF-kB activates CPI-17 in smooth muscle to regulate calcium sensitization and contractile force, a role in smooth muscle physiology.

    Evidence Promoter binding assays, EMSA, GATA6 siRNA, NF-kB KO mice, force measurement

    PMID:23275439

    Open questions at the time
    • Additive vs cooperative mechanism with NF-kB not fully dissected
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GATA6 switches between transcriptional activation and repression at different loci, and what cofactor/chromatin context dictates pioneer versus classical TF behavior, remains unresolved.
  • No unifying rule for activator-vs-repressor target selection
  • Structural basis of GATA6 cofactor complexes not determined
  • Post-translational modifications beyond S264 not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140110 transcription regulator activity 7 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 3

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GATA6 lies upstream of HNF4 in a transcriptional cascade regulating visceral endoderm differentiation; GATA6-null mice lack HNF4 expression in the endoderm, and forced GATA6 expression activates the HNF4 promoter in non-endodermal cells. GATA6-null embryoid bodies fail to form a visceral endoderm layer and lack expression of GATA4, AFP, and HNF3beta. Gene targeting (GATA6-null ES cells and mice), embryoid body differentiation, promoter activation assay, chimeric mouse analysis Genes & development High 9832509
2001 Overexpression of GATA6 in cardiomyocytes is sufficient to induce hypertrophic growth (increased cell surface area, sarcomeric organization, protein accumulation), and a dominant-negative GATA4-engrailed repressor blocks GATA6-directed transcriptional responses and agonist-induced hypertrophy, demonstrating that GATA6 is a necessary mediator of cardiomyocyte hypertrophy. Recombinant adenovirus overexpression in cardiomyocytes, dominant-negative fusion protein (GATA4-engrailed), transgenic mouse overexpression, cell surface area and protein accumulation measurements The Journal of biological chemistry High 11356841
2002 GATA6 is required for differentiation of alveolar epithelial type 1 cells in the distal lung; dominant-negative GATA6-Engrailed expression abolishes type 1 cells, increases Foxp2, and attenuates surfactant protein C expression. GATA6 can trans-activate the aquaporin-5 promoter, indicating direct transcriptional control of AT1-specific genes. Dominant-negative transgenic mice (GATA6-Engrailed driven by SP-C promoter), promoter trans-activation assay Development (Cambridge, England) High 11959831
2004 Endoderm differentiation and endoderm-specific gene expression (including laminin 1 subunits) in embryoid bodies is controlled by FGF-induced GATA6; GATA6-transformed Lamc1-null endoderm-like cells show that laminin 1 in the basement membrane subsequently induces epiblast differentiation. GATA6 overexpression in ES cells, embryoid body differentiation, pharmacological inhibitors (dominant-negative), gene expression analysis Development (Cambridge, England) Medium 15456727
2006 Gata6, but not Gata4, physically interacts with Nkx2.2 (an essential islet transcription factor). Dominant-negative Gata6-Engrailed expression in the pancreatic epithelium causes pancreatic agenesis or severe reduction of all pancreatic cell types, demonstrating Gata6 is an important regulator of pancreas specification. Co-immunoprecipitation (physical interaction with Nkx2.2), dominant-negative Gata6-Engrailed transgenic mice, histological analysis Developmental biology Medium 16887115
2006 Compound heterozygosity for GATA4 and GATA6 null alleles causes embryonic lethality with cardiovascular defects (thin-walled myocardium, septal defects), reduced cardiomyocyte proliferation, and downregulation of MEF2C and beta-myosin heavy chain, revealing a dosage threshold for GATA4/GATA6 activity in cardiovascular gene expression. Compound heterozygous mouse genetics, histology, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 16847256
2008 Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) by suppressing canonical Wnt signaling; loss of Gata6 increases canonical Wnt signaling and causes precocious BASC expansion. Gata6 regulates expression of the non-canonical Wnt receptor Fzd2, and increased Fzd2 or decreased beta-catenin rescues lung epithelial defects in Gata6 mutants. Conditional Gata6-null lung epithelium mice, genetic rescue (Fzd2 expression, beta-catenin reduction), Wnt signaling reporter assays, postnatal Gata6 deletion Nature genetics High 18536717
2008 Dynamic GATA6 expression distinguishes parietal endoderm (GATA6+) from visceral endoderm (GATA6 lost by E5.5). GATA6-null embryos fail to form a morphologically recognizable primitive endoderm layer, establishing GATA6 as essential for primitive endoderm formation at an earlier stage than previously recognized. Immunofluorescence, in situ hybridization, GATA6-null mouse embryo analysis Developmental dynamics Medium 18816845
2008 GATA6 and FOXA2 directly bind to the Wnt6 promoter and activate its transcription, linking GATA6 to canonical WNT-β-catenin pathway activation during primitive endoderm formation in F9 teratocarcinoma cells. Chromatin immunoprecipitation, luciferase reporter assay, overexpression of Gata6 and Foxa2 in F9 cells Stem cells and development Medium 22607194
2008 GATA6 activates calreticulin gene transcription by binding to site 1 on the calreticulin promoter (shown by EMSA and ChIP), while Evi-1 represses calreticulin and antagonizes GATA6-mediated activation at the same site. EMSA, chromatin immunoprecipitation, site-specific mutagenesis, reporter assays in neonatal cardiomyocytes and fibroblasts Biochemistry Medium 18303859
2009 siRNA-mediated reduction of GATA6 in human ovarian surface epithelial cells causes nuclear envelope deformation, failure of cytokinesis, and formation of polyploid/aneuploid cells. Loss of the nuclear envelope protein emerin mediates these consequences; direct siRNA suppression of emerin phenocopies GATA6 loss. siRNA knockdown, flow cytometry, immunofluorescence, nuclear morphology analysis Molecular and cellular biology Medium 19581290
2012 Simultaneous pancreas-specific deletion of both Gata4 and Gata6 causes severe pancreatic agenesis due to failure of progenitor cell proliferation, defects in branching morphogenesis, and loss of CPA1+ and NEUROG3+ progenitor differentiation; single deletion of either factor yields only mild defects that resolve postnatally. Conditional double knockout mice (Pdx1-Cre; Gata4fl/fl; Gata6fl/fl), histology, immunostaining, gene expression The Journal of clinical investigation High 23006325 23006330
2013 Endothelial GATA-6 directly transcriptionally regulates genes controlling vascular tone (endothelin-1, eNOS) and pro-inflammatory genes (CX3CL1, PAI-1, RhoB). Endothelial-specific Gata6 knockout mice spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, with innate immune cell infiltration. Endothelial-specific Gata6 conditional KO mice, pulmonary artery pressure measurement, histology, gene expression analysis The American journal of pathology Medium 23583651
2014 GATA6 levels regulate timing and speed of primitive endoderm (PrE) lineage commitment in the inner cell mass; GATA6 is necessary for PrE specification by FGF signaling; quantitative single-cell imaging shows that absence of GATA6 completely abolishes PrE and that GATA6 levels interact with NANOG and FGF/ERK to determine ICM fate. Quantitative single-cell-resolution image analysis, GATA6 hypomorphic and null embryos, FGF/ERK pathway manipulation Developmental cell High 24835466
2014 In mouse ICM, absence of GATA6 causes all cells to adopt epiblast identity, while absence of NANOG causes all cells to adopt PrE identity; these findings support a tristable regulatory network model where ERK signaling and concentrations of Nanog, Gata6, Fgf4, and Fgfr2 control ICM cell fate. Gata6-null and Gata6+/- embryo analysis, mathematical modeling, FGF/Erk pathway manipulation Development (Cambridge, England) Medium 25209243
2014 GATA6 directly enhances LGR5 expression, and miR-363 downregulates GATA6 thereby suppressing LGR5 and colorectal cancer tumourigenicity. The miR-363-GATA6-LGR5 axis is required for colorectal cancer tumorigenicity. Overexpression/knockdown assays, luciferase reporter assay (miR-363 targeting GATA6 3'UTR), in vivo xenograft Nature communications Medium 24452072
2014 GATA6 and GATA4 maintain pancreatic endoderm identity in part by repressing hedgehog signaling; in Gata4/Gata6 double-knockout pancreatic progenitors, hedgehog pathway components are ectopically upregulated, and GATA4/GATA6 can repress transcription through the Shh endoderm-specific enhancer MACS1, requiring GATA-binding sites within this enhancer. Double conditional KO mice (pDKO), reporter assay with MACS1 enhancer, GATA binding site mutagenesis Development (Cambridge, England) Medium 26932670
2014 GATA6 is a crucial regulator of Shh expression in the hindlimb bud; conditional Gata6 deletion from developing limbs causes ectopic Shh expression and preaxial polydactyly, and forced GATA6 expression represses Shh. GATA6 binds to regulatory elements of Shh and Gli1 in limb bud chromatin and represses their expression synergistically with FOG co-factors. Loss of Shh in Gata6-null limbs prevents polydactyly, placing GATA6 upstream of Shh. Conditional Gata6 KO (Prx1-Cre), forced Gata6 expression, ChIP, luciferase reporter assay, genetic epistasis (Shh/Gata6 double conditional KO) PLoS genetics High 24415953
2015 Gata6 is sufficient to initiate reprogramming of multiple cell types (pluripotent and differentiated neural cells) to induced extraembryonic endoderm stem cells. ChIP-seq shows GATA6 enrichment near both pluripotency and endoderm genes, functioning as a direct repressor of pluripotency genes (Nanog, Esrrb, Sox2, Oct4) and activator of ExEn genes in a stepwise manner. Inducible Gata6 expression, cell reprogramming assays, ChIP-seq, transcriptional profiling Genes & development High 26109048
2015 Gata6 maintains acinar differentiation and suppresses KrasG12V-driven pancreatic tumorigenesis; ChIP-seq and RNA-seq show that GATA6 directly represses the EGFR pathway and inflammatory pathways in the pancreas; Gata6 ablation renders acinar cells more sensitive to KRas(G12V) and accelerates tumor development. Genetically engineered mouse models, ChIP-seq, RNA-seq, GATA6 silencing in human PDAC cells Gut High 25596178
2016 GATA6 inhibits epithelial-mesenchymal transition (EMT) in pancreatic cancer cells in vitro and cell dissemination in vivo; GATA6 ChIP-seq and RNA-seq demonstrate direct transcriptional regulation of EMT-related genes and indirect regulation through other EMT transcription factors. GATA6 silencing and overexpression in PDAC cell lines, ChIP-seq, RNA-seq, in vivo dissemination assay Gut High 27325420
2016 Gata6 controls the renewal of rapidly proliferating hair follicle matrix progenitor cells by protecting against DNA damage associated with proliferation; Gata6 stimulates Edaradd expression and NF-κB pathway activation, and Edaradd rescues DNA damage, cell survival, proliferation, and MCM10 expression in Gata6-null keratinocytes. Conditional Gata6 KO mice, cultured keratinocyte rescue experiments with Edaradd, DNA damage assays, gene expression analysis The EMBO journal Medium 27908934
2017 Gata6 controls the identity of the sebaceous duct lineage and specifies a lineage switch between sebocytes and SD cells; during wound healing, differentiated Gata6+ cells migrate from the sebaceous duct into the interfollicular epidermis and dedifferentiate, acquiring long-term self-renewal ability and multilineage differentiation capacity. Conditional Gata6 KO mice, lineage tracing, live imaging, clonogenic assays Nature cell biology High 28504705
2017 GATA6 is required for normal insulin biosynthesis and secretion in adult β-cells; pancreas-specific Gata6 inactivation causes glucose intolerance, decreased insulin content, impaired insulin secretion, and ultrastructural abnormalities in β-cells. Pdx1 expression in adult β-cells depends on GATA-binding sites, and GATA6 loss greatly affects β-cell-specific gene expression. Pancreas-specific Gata6 KO mice, glucose tolerance testing, insulin secretion assays, electron microscopy, transgenic reporter mice with GATA site mutations Diabetes High 29263149
2017 GATA6 and Sp1 interact and cooperatively activate Aqp5 transcription via histone H3 acetylation; GATA6 competes with HDAC3 for Sp1 binding, and p300 modulates H3 acetylation through interactions with GATA6/Sp1. GATA6 knockdown decreases AQP5 expression in alveolar epithelial cells. siRNA knockdown, HDAC inhibitor treatment, Co-IP (GATA6/Sp1/p300/HDAC3 interactions), ChIP for histone acetylation, reporter assays Scientific reports Medium 28615712
2018 Phosphorylation of GATA6 at a conserved serine residue (S264) by Erk1/2 is required for GATA6 to activate its own promoter and drive a positive feedback loop for primitive endoderm differentiation; S264 mutations drastically impair GATA6's ability to activate its own promoter in ES cells. Gata6-H2BGFP knock-in mouse, ES cell differentiation, site-directed mutagenesis of S264, promoter activation assay Developmental biology High 29454706
2018 Gata6 haploinsufficiency causes highly penetrant right-left-type bicuspid aortic valve in mice. Mechanistically, Gata6 haploinsufficiency disrupts valve remodeling and extracellular matrix composition through dysregulation of MMP9. Cell-specific inactivation reveals that GATA6 is required specifically in secondary heart field (Isl-1-positive) myocytes, not endothelial or neural crest cells, for aortic valve formation. Gata6 heterozygous mice, cell-specific conditional KO (Isl-1-Cre, endothelial-Cre, neural crest-Cre), MMP9 expression analysis, human GWAS validation Circulation High 29567669
2018 In endometriosis, GATA6 is necessary for CYP17A1-mediated conversion of progesterone to androstenedione in endometriotic cells, and simultaneous expression of both GATA6 and NR5A1 is required and sufficient to activate all five steroidogenic genes (HSD3B2, CYP17A1, CYP19A1 and others) and estradiol production in normal endometrial stromal cells. Ectopic expression and siRNA knockdown of GATA6 and NR5A1 in endometrial and endometriotic stromal cells, estradiol ELISA, RT-qPCR, western blot Reproductive sciences Medium 29402198
2019 GATA6 cooperates with EOMES/SMAD2/3 to regulate cardinal endoderm gene expression at the genome-wide level; GATA6-null human PSCs fail to enter the definitive endoderm lineage, while heterozygous cells show modest DE reduction, explaining the human-specific pancreatic agenesis with heterozygous GATA6 mutations. Gene-edited and patient-derived hPSCs, directed differentiation, ChIP-seq (GATA6, EOMES, SMAD2/3), RNA-seq, flow cytometry Stem cell reports High 30629940
2019 GATA6 directly upregulates CD137L (TNFSF9) expression in cutaneous T-cell lymphoma cells by binding to its promoter; GATA6 overexpression in CTCL is driven by DNA hypomethylation and histone acetylation, and GATA6 inhibition decreases CTCL cell survival and in vivo growth. ChIP assay, luciferase reporter assay, shRNA knockdown, flow cytometry, in vivo mouse xenograft Blood Medium 30194255
2019 GATA6 directly transcribes miR-520b (shown by luciferase reporter and ChIP assays), and miR-520b suppresses CREB1, establishing a GATA6/miR-520b/CREB1 axis that suppresses gastric cancer cell migration and metastasis. Luciferase reporter assay, ChIP, overexpression/knockdown, in vivo metastasis model Cell death & disease Medium 30674866
2019 GATA6 directly binds the promoter of the PKM gene and regulates PKM2 transcription; GATA6 silencing in HCC cells promotes glycolytic metabolism, EMT, tumorigenicity, and self-renewal via PKM2 upregulation. ChIP assay, gene knockdown and overexpression, metabolic assays (glucose uptake), in vivo tumorigenicity International journal of cancer Medium 30834518
2019 GATA6 physically interacts with LOXL2 (the scavenger receptor cysteine-rich domain of LOXL2 interacts with GATA6), and this complex promotes VEGFA mRNA expression and protein secretion, driving angiogenesis and tube formation in cholangiocarcinoma. Co-immunoprecipitation, western blot, RT-qPCR, ELISA, tube formation assay, in vivo xenograft International journal of oncology Medium 31322171
2019 Gata4 directly represses Gata6 transcription through responsive repressive sites within 1 kb upstream of the Gata6 transcription start site, shown by ChIP-qPCR and luciferase reporter assay; enhanced Gata6 expression in Gata4 heterozygous SHF cells contributes to outflow tract defects. ChIP-qPCR, luciferase reporter assay, Gata4 heterozygous mouse model, gene expression analysis PLoS genetics Medium 31120883
2020 GATA6 is a pioneer factor in cardiac development: it regulates SMYD1 (which activates HAND2) and KDR (which with HAND2 orchestrates outflow tract formation). GATA6 loss-of-function variants perturb cardiac and endoderm lineage genes directing PDX1/pancreatic development. An exon 4 GATA6 missense variant causes ectopic pioneer activities, reducing GATA4, FOXA1/2, and PDX1 and increasing retinoic acid signaling promoting diaphragm development. Isogenic iPSC cardiomyocyte differentiation, RNA-seq, ATAC-seq (chromatin accessibility), ChIP-seq, GATA6 LoF and missense variant comparison eLife High 33054971
2020 EZH2 transcriptionally represses GATA6 in PDAC via H3K27 methylation; genetic or pharmacologic EZH2 depletion increases GATA6 expression and induces a classical gene signature, while GATA6 re-ablation in EZH2-deficient cells rescues invasive capacity and basal gene signature. ChIP-seq (EZH2 on GATA6 locus), RNA-seq, GATA6 knockdown in EZH2-depleted cells, transgenic PDAC models Cancer research High 32907838
2020 GATA6 directly binds the promoter of VEGF-C at its promoter region and acts as a transcriptional repressor; loss of GATA6 in bladder cancer (via promoter hypermethylation) leads to VEGF-C upregulation, promoting lymphangiogenesis and lymph node metastasis. ChIP assay, promoter binding assay, GATA6 reconstitution and knockdown, in vivo lymph node metastasis model FASEB journal Medium 32103545
2020 GATA6 directly upregulates MUC1 expression by binding to GATA-motifs at positions -1584 and -1456 in the MUC1 promoter; MUC1 then binds to β-catenin and increases nuclear β-catenin levels, driving EMT and metastasis in cholangiocarcinoma. ChIP-seq, luciferase reporter assay with point-mutant GATA sites, co-immunoprecipitation (MUC1/β-catenin), knockdown/overexpression, in vivo metastasis Cell death & disease Medium 33060563
2020 GATA6 controls insulin biosynthesis/secretion in adult β-cells and lung specification from human PSCs: knockdown of GATA6 during endoderm patterning increases NKX2.1+ lung progenitors, while GATA6 ablation impairs terminal lung differentiation; transgenic GATA6 expression skews development toward liver fate at the expense of lung progenitors, revealing a dosage effect. GATA6 knockdown and null hPSC lines, directed differentiation to lung progenitors, flow cytometry, gene expression analysis The Journal of clinical investigation Medium 29889101
2020 TET2 marks the GATA6 locus with 5-hydroxymethylcytosine (5hmc) to maintain classical PDAC phenotype; SMAD4 directly supports TET2 levels, and loss of SMAD4 reduces 5hmc, GATA6 expression, and promotes squamous-like tumors. Restoring TET2 stability with metformin/vitamin C restores 5hmc and GATA6 levels and reverts squamous-like phenotype in vitro and in vivo. Oxidative bisulfite sequencing (genome-wide 5hmc and 5mc mapping), in vivo pharmacological rescue, bioinformatics iCluster Gastroenterology Medium 33915173
2021 HDAC1/2 suppress GATA6 expression by promoting STAT3 acetylation, which enhances DNMT1 binding to STAT3 and leads to hypermethylation of the GATA6 promoter CpG region (+140/+255); blocking STAT3 acetylation at Lys685 disrupts DNMT1-STAT3 interaction and reverses GATA6 promoter methylation, demonstrating an epigenetic regulatory mechanism for GATA6 in endothelial cells. Romidepsin treatment, HDAC1/2 siRNA, methylation-specific PCR, ChIP (STAT3 enrichment at GATA6 promoter), STAT3 Lys685Arg mutation, Co-IP (DNMT1-STAT3), in vivo atherosclerosis model Theranostics Medium 33859766
2021 A GATA6-centered gene regulatory network involving HNF1A and HNF4A controls PDAC subtype identity; GATA6 loss alone is necessary but not sufficient for basal program expression—concomitant loss of HNF1A and HNF4A (through epigenetic silencing) is required for the full phenotype switch. In mice, late Gata6 deletion dramatically increased metastatic rate. Dual-recombinase mouse model (Gata6LateKO), RNA-seq of primary tumor cells, human transcriptomics datasets, tissue samples Gut High 33846140
2021 GATA6 directly activates TBX3 and EDN1 as key regulators of the sinus node genetic program (in conduction and non-conduction cells, respectively); Gata6 haploinsufficiency causes hypoplastic sinus node and rhythm abnormalities, and cell-specific deletion reveals requirements in multiple SAN lineages. Gata6 heterozygous and cell-specific conditional KO mice, ECG recording, histology, chromatin binding and transcriptional activation assays Proceedings of the National Academy of Sciences of the United States of America High 33443158
2022 GATA6 and NANOG co-bind at the vast majority of epiblast and PrE enhancers both in embryonic stem cells and in blastocysts; upon GATA6 induction, co-binding is followed by eviction of Epi TFs, rapid chromatin remodeling and remodeling of enhancer-promoter contacts to establish PrE lineage while repressing Epi fate. Inducible GATA6 in ES cells, ChIP-seq (GATA6 and NANOG), ATAC-seq, Hi-C/4C (enhancer-promoter contacts), blastocyst ChIP Nature communications High 35871075
2022 EP300 (p300) histone acetyltransferase directly supports GATA6 expression; loss of EP300 downregulates GATA6 and silences the GATA6-regulated differentiation program, causing a phenotypic switch from classical to basal-like/squamous PDAC subtype and resistance to PORCN (Wnt) inhibitors. In vivo CRISPR screen, EP300 knockdown/KO, GATA6 overexpression rescue, RNA-seq, chromatin accessibility mapping The Journal of clinical investigation High 35536676
2022 Endothelial Gata6 deletion reduces atherosclerosis by decreasing monocyte infiltration and pro-inflammatory macrophage formation; Cmpk2 and Ccl5 are identified as direct target genes of GATA6 in endothelial cells mediating these effects through the CMPK2-Nlrp3 pathway. EC-specific Gata6 KO in ApoeKO mice, endothelial AAV9-Cmpk2-shRNA delivery, ChIP (direct target identification), monocyte adhesion and migration assays, lesion quantification Redox biology Medium 37339559
2023 Gata6 deletion from the brown fat lineage causes a striking loss of brown adipose tissue, identifying GATA6 as a crucial regulator of brown adipocyte development; GATA6 marks brown adipogenic progenitor cells. Single-cell gene expression analysis, immunostaining, lineage tracing, conditional Gata6 KO in brown fat lineage Developmental cell Medium 37647897
2023 SIRT6 inhibits GATA6 transcription by deacetylating and increasing degradation of the transcription factor Nkx2.5 (which would otherwise activate GATA6); GATA6 in turn impedes ATM-mediated DNA damage repair, leading to accelerated VSMC senescence and osteogenic differentiation. Gata6 knockdown (via AAV-shRNA) inhibits arterial calcification in CKD mice. SIRT6-transgenic mice, Gata6 AAV-shRNA knockdown, in vitro gain/loss-of-function, co-immunoprecipitation (SIRT6-Nkx2.5), DNA damage repair assays (ATM pathway) Kidney international Medium 37914087
2012 GATA-6 and NF-κB bind to specific sites on the CPI-17 promoter and upregulate CPI-17 expression in an additive manner in bladder smooth muscle cells; CPI-17 inhibits myosin light chain phosphatase, thereby regulating Ca2+ sensitization and contractile force maintenance in smooth muscle. Promoter binding assays, EMSA, GATA-6 siRNA knockdown, NF-κB KO mice, smooth muscle force measurement Molecular and cellular biology Medium 23275439
2016 Gain-of-function GATA6 variants (R585L, P91S, A177T) show markedly upregulated transcriptional activity in reporter assays and enhanced activation of ANP and alpha-MHC promoters when co-expressed with GATA4 and MEF2C, demonstrating that gain-of-function GATA6 mutations can drive atrial fibrillation. Whole exome sequencing, luciferase reporter assay with wild-type and mutant GATA6 constructs, co-expression with GATA4/MEF2C Heart rhythm Medium 27756709
2015 REG4 is a direct transcriptional target of GATA6; GATA6-mediated activation of REG4 enhances adherent growth of colon cancer cells, while LGR5 activation by GATA6 drives clonogenicity, with both being suppressed by miR-363 targeting of GATA6. GATA6 overexpression/knockdown, miR-363 overexpression, gene expression analysis, colon cancer cell proliferation/tumorigenicity assays Scientific reports Medium 26387746

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes & development 534 9832509
2001 The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. The Journal of biological chemistry 301 11356841
2020 GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 282 32156747
2008 A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nature genetics 229 18536717
2016 GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut 219 27325420
2014 GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Developmental cell 179 24835466
1997 Expression and hormonal regulation of transcription factors GATA-4 and GATA-6 in the mouse ovary. Endocrinology 179 9231805
2014 Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. The Journal of experimental medicine 175 25024137
2014 Gata6, Nanog and Erk signaling control cell fate in the inner cell mass through a tristable regulatory network. Development (Cambridge, England) 170 25209243
1999 Expression and regulation of transcription factors GATA-4 and GATA-6 in developing mouse testis. Endocrinology 169 10067876
2006 A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Proceedings of the National Academy of Sciences of the United States of America 166 16847256
2020 miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer. Proceedings of the National Academy of Sciences of the United States of America 147 32041891
2017 Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties. Nature cell biology 134 28504705
2012 Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. The Journal of clinical investigation 130 23006325
2012 GATA4 and GATA6 control mouse pancreas organogenesis. The Journal of clinical investigation 125 23006330
2002 GATA6 regulates differentiation of distal lung epithelium. Development (Cambridge, England) 119 11959831
2020 HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell reports 113 32402285
2015 Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells. Genes & development 103 26109048
2006 Gata6 is an important regulator of mouse pancreas development. Developmental biology 96 16887115
2010 A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. Journal of human genetics 95 20631719
2011 GATA5 interacts with GATA4 and GATA6 in outflow tract development. Developmental biology 87 21839733
2014 The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis. Nature communications 86 24452072
2015 The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice. Gut 76 25596178
2021 A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer. Gut 73 33846140
2018 GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic Valve. Circulation 72 29567669
2008 Dynamic GATA6 expression in primitive endoderm formation and maturation in early mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 72 18816845
2004 Distinct GATA6- and laminin-dependent mechanisms regulate endodermal and ectodermal embryonic stem cell fates. Development (Cambridge, England) 70 15456727
2020 EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6. Cancer research 69 32907838
2014 GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development. Developmental biology 62 24929016
2007 GATA6 is an astrocytoma tumor suppressor gene identified by gene trapping of mouse glioma model. Proceedings of the National Academy of Sciences of the United States of America 61 17463088
2016 GATA4 and GATA6 regulate pancreatic endoderm identity through inhibition of hedgehog signaling. Development (Cambridge, England) 59 26932670
2009 Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer. Molecular and cellular biology 58 19581290
2012 MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma. BMC cancer 52 22672670
2020 Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis. Nature communications 51 33082341
2020 GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm. eLife 48 33054971
2021 HDAC1 and 2 regulate endothelial VCAM-1 expression and atherogenesis by suppressing methylation of the GATA6 promoter. Theranostics 47 33859766
2023 The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair. Kidney international 46 37914087
2021 TET2 Drives 5hmc Marking of GATA6 and Epigenetically Defines Pancreatic Ductal Adenocarcinoma Transcriptional Subtypes. Gastroenterology 44 33915173
2019 GATA6 Cooperates with EOMES/SMAD2/3 to Deploy the Gene Regulatory Network Governing Human Definitive Endoderm and Pancreas Formation. Stem cell reports 43 30629940
2018 GATA6 loss-of-function mutation contributes to congenital bicuspid aortic valve. Gene 42 29653232
2014 GATA6 is a crucial regulator of Shh in the limb bud. PLoS genetics 42 24415953
2023 Gata6+ large peritoneal macrophages: an evolutionarily conserved sentinel and effector system for infection and injury. Trends in immunology 41 36623953
2015 REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis. Scientific reports 41 26387746
2022 Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages. Nature communications 40 35871075
2021 Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis. Basic research in cardiology 40 33876316
2020 GATA6 promotes epithelial-mesenchymal transition and metastasis through MUC1/β-catenin pathway in cholangiocarcinoma. Cell death & disease 39 33060563
2012 GATA6 loss-of-function mutation in atrial fibrillation. European journal of medical genetics 38 22750565
2021 The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer. Scientific reports 37 34294813
2016 Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation. The EMBO journal 37 27908934
2022 Gata6+ resident peritoneal macrophages promote the growth of liver metastasis. Nature communications 35 35906202
2018 miR-196b promotes lung cancer cell migration and invasion through the targeting of GATA6. Oncology letters 35 29928408
2022 A p300/GATA6 axis determines differentiation and Wnt dependency in pancreatic cancer models. The Journal of clinical investigation 34 35536676
2013 Endothelial GATA-6 deficiency promotes pulmonary arterial hypertension. The American journal of pathology 34 23583651
2019 The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma. International journal of oncology 33 31322171
2018 Aberrant CD137 ligand expression induced by GATA6 overexpression promotes tumor progression in cutaneous T-cell lymphoma. Blood 33 30194255
2007 Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. Molecular and cellular endocrinology 33 17337116
2022 GATA4 and GATA6 loss-of-expression is associated with extinction of the classical programme and poor outcome in pancreatic ductal adenocarcinoma. Gut 32 36109153
2020 Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 32 33318580
2018 The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 32 29402198
2020 GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation. Stem cell reports 31 32795420
2020 GATA6 regulates aging of human mesenchymal stem/stromal cells. Stem cells (Dayton, Ohio) 31 33252174
2019 GATA6 suppresses migration and metastasis by regulating the miR-520b/CREB1 axis in gastric cancer. Cell death & disease 31 30674866
2017 Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer. Oncogene 30 29106391
2023 Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways. Redox biology 29 37339559
2019 Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers. Clinical genetics 28 31437305
2017 Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation. Scientific reports 28 28615712
2022 GATA6 Deficiency Leads to Epithelial Barrier Dysfunction and Enhances Susceptibility to Gut Inflammation. Journal of Crohn's & colitis 27 34374415
2018 GATA6 phosphorylation by Erk1/2 propels exit from pluripotency and commitment to primitive endoderm. Developmental biology 27 29454706
2012 GATA6 and FOXA2 regulate Wnt6 expression during extraembryonic endoderm formation. Stem cells and development 26 22607194
2001 Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression. Mechanisms of development 26 11429286
2023 GATA6-AS1 Regulates Intestinal Epithelial Mitochondrial Functions, and its Reduced Expression is Linked to Intestinal Inflammation and Less Favourable Disease Course in Ulcerative Colitis. Journal of Crohn's & colitis 25 36655602
2014 Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2. Respiratory research 25 24970044
2021 lncRNA TUG1 Facilitates Colorectal Cancer Stem Cell Characteristics and Chemoresistance by Enhancing GATA6 Protein Stability. Stem cells international 24 34858502
2020 Loss of GATA6 expression promotes lymphatic metastasis in bladder cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32103545
2015 Adrenal Development in Mice Requires GATA4 and GATA6 Transcription Factors. Endocrinology 24 25933105
2019 Mutant Lef1 controls Gata6 in sebaceous gland development and cancer. The EMBO journal 23 30886049
2019 LncRNA GATA6-AS Promotes Cancer Cell Proliferation and Inhibits Apoptosis in Glioma by Downregulating lncRNA TUG1. Cancer biotherapy & radiopharmaceuticals 23 31809214
2023 Control of murine brown adipocyte development by GATA6. Developmental cell 22 37647897
2022 IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6. The international journal of biochemistry & cell biology 22 36113831
2020 GATA6 is a regulator of sinus node development and heart rhythm. Proceedings of the National Academy of Sciences of the United States of America 22 33443158
2017 miR-124 targets GATA6 to suppress cholangiocarcinoma cell invasion and metastasis. BMC cancer 22 28270130
2017 GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells. Diabetes 22 29263149
2008 Regulation of the calreticulin gene by GATA6 and Evi-1 transcription factors. Biochemistry 22 18303859
2005 Expression of GATA6 in the human and mouse central nervous system. Brain research. Developmental brain research 22 16150495
2023 GATA6 and CK5 Stratify the Survival of Patients With Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 36788090
2019 Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development. PLoS genetics 21 31120883
2016 Gain-of-function mutations in GATA6 lead to atrial fibrillation. Heart rhythm 21 27756709
2023 GATA6 Inhibits Neuronal Autophagy and Ferroptosis in Cerebral ischemia-reperfusion Injury Through a miR-193b/ATG7 axis-dependent Mechanism. Neurochemical research 20 37059928
2012 GATA-6 and NF-κB activate CPI-17 gene transcription and regulate Ca2+ sensitization of smooth muscle contraction. Molecular and cellular biology 20 23275439
2020 A long non-coding RNA GATA6-AS1 adjacent to GATA6 is required for cardiomyocyte differentiation from human pluripotent stem cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32888237
2019 Deregulated GATA6 modulates stem cell-like properties and metabolic phenotype in hepatocellular carcinoma. International journal of cancer 18 30834518
2019 GATA6-upregulating autophagy promotes TKI resistance in nonsmall cell lung cancer. Cancer biology & therapy 18 31092103
2024 GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery. Cell reports. Medicine 17 38733987
2019 GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions. American journal of reproductive immunology (New York, N.Y. : 1989) 17 30589192
2018 Loss of Gata6 causes dilation of the hair follicle canal and sebaceous duct. Experimental dermatology 16 30033638
2007 A role for GATA-6 in vertebrate chondrogenesis. Developmental biology 16 18191120
2023 Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation. Nature cell biology 15 37735598
2018 GATA6 suppression enhances lung specification from human pluripotent stem cells. The Journal of clinical investigation 15 29889101
2016 Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats. Gene 15 27511375
2014 Activated protease receptor-2 induces GATA6 expression to promote survival in irradiated colon cancer cells. Archives of biochemistry and biophysics 15 24887481

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