GATA4 is a GATA-family zinc-finger transcription factor with two GATA-type C4 zinc fingers; the C-terminal finger recognizes (A/T)GATA(A/G) motifs in promoters and enhancers and the N-terminal finger stabilizes DNA binding and recruits FOG cofactors (ZFPM2/FOG2). It is a nuclear, predominantly activating RNA polymerase II transcription factor that can engage its sites in compacted chromatin, and it acts combinatorially with partner DNA-binding factors (NKX2-5, TBX5, SMAD4, NR5A1, MEF2, HAND2) and coregulators to drive tissue-specific gene programs such as NPPA/NPPB in heart and AMH/SRY in gonad. In the heart GATA4 is expressed in precardiac mesoderm, myocardium and endocardium, where it promotes cardiomyocyte proliferation and survival, right ventricle and atrioventricular canal/endocardial cushion morphogenesis and septation; heterozygous mutations cause atrial, ventricular and atrioventricular septal defects, tetralogy of Fallot and bicuspid aortic valve. GATA4 also acts in endoderm derivatives (foregut, liver bud, ventral pancreas, intestinal epithelium) and, with FOG2 and NR5A1, in Sertoli cells for testis determination and differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: negative regulation of transcription by RNA polymerase II, inherited from the GATA family node. Reason: GATA4 is predominantly an activator, but genome-wide studies in human iPSC-cardiomyocytes show that GATA4 together with TBX5 is needed to repress non-cardiac (endothelial/endocardial) genes, and FOG2 can convert GATA4 into a repressor on some promoters. The family-level IBA is therefore biologically sound for GATA4, but repression is secondary to its activator role. Supporting Evidence: PMID:27984724 the GATA4-G296S mutation led to failure of GATA4 and TBX5-mediated repression at non-cardiac genes |
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: GATA4 is located on chromatin (electronic / TFClass-based assignment). Reason: ChIP-seq in human cardiomyocytes shows GATA4 broadly occupying cardiac enhancers, and GATA4 can bind its sites even in compacted nucleosomal chromatin. Chromatin is the appropriate location for a sequence-specific transcription factor. Supporting Evidence: PMID:27984724 In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5 PMID:11864602 HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: GATA4 is located on chromatin (electronic / TFClass-based assignment). Reason: ChIP-seq in human cardiomyocytes shows GATA4 broadly occupying cardiac enhancers, and GATA4 can bind its sites even in compacted nucleosomal chromatin. Chromatin is the appropriate location for a sequence-specific transcription factor. Supporting Evidence: PMID:27984724 In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5 PMID:11864602 HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | ACCEPT | Summary: IDA from a study showing GATA-4/5/6 directly activate the intestinal IFABP promoter via a proximal promoter element. Reason: The function (binding cis-regulatory DNA) is correct for GATA4; the more specific GO:0000978 is also annotated. The cached abstract describes the experiments with Xenopus GATA-4, but the curator had the full text and the activity is conserved, so the annotation is retained. Supporting Evidence: PMID:9566909 We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal fatty acid-binding protein (xIFABP) gene |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to transcription cis-regulatory region binding. Reason: Correct, if less specific than GO:0000978; GATA4 binds GATA elements in promoters such as AMH and NPPA. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic annotation to Pol II transcription regulatory region sequence-specific DNA binding. Reason: Correct; GATA4 binds GATA motifs in Pol II promoters/enhancers (AMH promoter EMSA). Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IGI PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: IGI from Gata4/Smad4 genetic interaction and cooperative activation of the Id2 promoter. Reason: Gata4 and Smad4 cooperatively activate the Id2 promoter, which contains a putative Gata4 site, and human GATA4 mutations abolish this; consistent with Pol II regulatory region binding. The finer-grained GO:0000978 is also present. Supporting Evidence: PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding. Reason: Core molecular function. EMSA shows human GATA4 binding the GATA4-responsive element of the AMH promoter, and disease mutations in the zinc fingers reduce DNA-binding affinity. Conserved across the GATA family (IBA). Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | ACCEPT | Summary: IDA (EMSA) showing wild-type GATA4 binds the GATA element in the AMH promoter, lost in the p.Gly221Arg mutant. Reason: Core molecular function. EMSA shows human GATA4 binding the GATA4-responsive element of the AMH promoter, and disease mutations in the zinc fingers reduce DNA-binding affinity. Conserved across the GATA family (IBA). Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding. Reason: Core molecular function. EMSA shows human GATA4 binding the GATA4-responsive element of the AMH promoter, and disease mutations in the zinc fingers reduce DNA-binding affinity. Conserved across the GATA family (IBA). Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Core function. GATA4 is a sequence-specific (A/T)GATA(A/G) DNA-binding transcription factor that activates RNA polymerase II target genes; patient mutations reduce both DNA binding and transactivation. This is also the module annoton function for GATA4 in the cardiac specification network. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Core function. GATA4 is a sequence-specific (A/T)GATA(A/G) DNA-binding transcription factor that activates RNA polymerase II target genes; patient mutations reduce both DNA binding and transactivation. This is also the module annoton function for GATA4 in the cardiac specification network. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Core function. GATA4 is a sequence-specific (A/T)GATA(A/G) DNA-binding transcription factor that activates RNA polymerase II target genes; patient mutations reduce both DNA binding and transactivation. This is also the module annoton function for GATA4 in the cardiac specification network. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic annotation to cis-regulatory region sequence-specific DNA binding. Reason: Correct parent of the core GO:0000978 annotation. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0001216 DNA-binding transcription activator activity | IDA PMID:29325903 GATA4 Loss-of-Function Mutation and the Congenitally Bicuspi... | ACCEPT | Summary: IDA from luciferase assays showing GATA4 transactivation is lost with the E147X truncation. Reason: GATA4 is a transcriptional activator; the Pol II-specific child GO:0001228 is also annotated. Supporting Evidence: PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0001223 transcription coactivator binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic annotation (Ensembl Compara) to transcription coactivator binding. Reason: GATA4 recruits coactivators/cofactors (e.g. EP300 per UniProt, FOG2, GLYR1, BRD4). Plausible but the transferred evidence is not reviewed here; the informative core partner binding is to DNA-binding TFs (GO:0061629). Supporting Evidence: PMID:35182466 BRD4 and SMARCC1, CHD candidate genes and GATA4 interactors |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific. Reason: GATA4 activates Pol II promoters (AMH, Id2, NPPA) through bound GATA sites, alone and synergistically with NR5A1, SMAD4, NKX2-5 and TBX5. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IGI PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific. Reason: GATA4 activates Pol II promoters (AMH, Id2, NPPA) through bound GATA sites, alone and synergistically with NR5A1, SMAD4, NKX2-5 and TBX5. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity |
| GO:0001947 heart looping | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Heart looping, transferred from mouse Gata4. Reason: Gata4-null mouse embryos fail to form a single ventral heart tube because of a ventral folding defect, so looping cannot be assessed directly there; looping/morphogenesis phenotypes in partially deficient models are downstream of GATA4's transcriptional role in myocardial growth. Retained as non-core developmental annotation from mouse curation. Supporting Evidence: PMID:9136933 Mutant embryos most notably lacked a primitive heart tube and foregut |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Heart looping, transferred from mouse Gata4. Reason: Gata4-null mouse embryos fail to form a single ventral heart tube because of a ventral folding defect, so looping cannot be assessed directly there; looping/morphogenesis phenotypes in partially deficient models are downstream of GATA4's transcriptional role in myocardial growth. Retained as non-core developmental annotation from mouse curation. Supporting Evidence: PMID:9136933 Mutant embryos most notably lacked a primitive heart tube and foregut |
| GO:0003007 heart morphogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic annotation to heart morphogenesis. Reason: Myocardial Gata4 deletion and hypomorphic alleles cause RV hypoplasia, common AV canal and DORV; human GATA4 mutations cause septal and valve defects. Supporting Evidence: PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. |
| GO:0003162 atrioventricular node development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | UNDECIDED | Summary: NAS from a review of cardiac conduction system development. Reason: The cached record of this review is abstract-only and does not mention GATA4; GATA4 has been implicated in AV conduction-system gene regulation but I could not verify the specific statement the curator relied on. Supporting Evidence: PMID:26786210 CCS development involves complex regulatory networks that act in stage-, tissue- and dose-dependent manners |
| GO:0003180 aortic valve morphogenesis | IMP PMID:29325903 GATA4 Loss-of-Function Mutation and the Congenitally Bicuspi... | KEEP AS NON CORE | Summary: IMP from a familial bicuspid aortic valve GATA4 E147X loss-of-function mutation. Reason: Human genetic and reporter data link GATA4 loss of function to BAV; mouse Gata4 ki (FOG-binding mutant) embryos also have semilunar valve defects. A genuine but downstream developmental role. Supporting Evidence: PMID:29325903 this study associates the GATA4 loss-of-function mutation with enhanced susceptibility to a BAV PMID:11297508 semilunar cardiac valve defects and a double-outlet right ventricle |
| GO:0003190 atrioventricular valve formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Atrioventricular valve formation (mouse transfer). Reason: Endocardial Gata4 cooperates with Smad4 in atrioventricular valve formation; secondary to its endocardial cushion role. Supporting Evidence: PMID:21330551 From these results we deduced that Gata4 and Smad4 genetically cooperate in the endocardium during atrioventricular valve formation. |
| GO:0003190 atrioventricular valve formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrioventricular valve formation (mouse transfer). Reason: Endocardial Gata4 cooperates with Smad4 in atrioventricular valve formation; secondary to its endocardial cushion role. Supporting Evidence: PMID:21330551 From these results we deduced that Gata4 and Smad4 genetically cooperate in the endocardium during atrioventricular valve formation. |
| GO:0003197 endocardial cushion development | IEA GO_REF:0000107 | ACCEPT | Summary: Endocardial cushion development. Reason: Early myocardial Gata4 deletion abolishes cushion mesenchyme; endothelial Gata4/Smad4 compound heterozygotes develop AV septal defects, and GATA4-SMAD4 cooperatively activate Id2 in the cushions. One of the best-supported specific cardiac roles. Supporting Evidence: PMID:15902305 Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. PMID:21330551 atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency |
| GO:0003197 endocardial cushion development | IMP PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: IMP: endothelial-specific Gata4/Smad4 compound haploinsufficiency causes AV septal defects. Reason: Early myocardial Gata4 deletion abolishes cushion mesenchyme; endothelial Gata4/Smad4 compound heterozygotes develop AV septal defects, and GATA4-SMAD4 cooperatively activate Id2 in the cushions. One of the best-supported specific cardiac roles. Supporting Evidence: PMID:15902305 Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. PMID:21330551 atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency |
| GO:0003197 endocardial cushion development | ISS GO_REF:0000024 | ACCEPT | Summary: Endocardial cushion development. Reason: Early myocardial Gata4 deletion abolishes cushion mesenchyme; endothelial Gata4/Smad4 compound heterozygotes develop AV septal defects, and GATA4-SMAD4 cooperatively activate Id2 in the cushions. One of the best-supported specific cardiac roles. Supporting Evidence: PMID:15902305 Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. PMID:21330551 atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency |
| GO:0003208 cardiac ventricle morphogenesis | TAS PMID:20347099 A novel mutation in GATA4 gene associated with dominant inhe... | ACCEPT | Summary: TAS to cardiac ventricle morphogenesis citing a familial ASD mutation paper. Reason: The cited paper concerns atrial septal defect and does not itself address ventricle morphogenesis, but the term is well supported for GATA4 by mouse myocardial deletion (RV hypoplasia, DORV) and hypomorphic alleles. Supporting Evidence: PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. |
| GO:0003215 cardiac right ventricle morphogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Cardiac right ventricle morphogenesis (mouse transfer). Reason: Early myocardial deletion of Gata4 causes selective RV hypoplasia associated with loss of Hand2 expression. Supporting Evidence: PMID:15902305 Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. |
| GO:0003215 cardiac right ventricle morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: Cardiac right ventricle morphogenesis (mouse transfer). Reason: Early myocardial deletion of Gata4 causes selective RV hypoplasia associated with loss of Hand2 expression. Supporting Evidence: PMID:15902305 Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. |
| GO:0003279 cardiac septum development | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic annotation to cardiac septum development. Reason: Heterozygous GATA4 mutations cause atrial, ventricular and atrioventricular septal defects in humans. Supporting Evidence: PMID:12845333 These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 |
| GO:0003281 ventricular septum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ventricular septum development (mouse transfer). Reason: Supported by VSD in human GATA4 mutation carriers and DORV/CAVC in hypomorphic mice, but atrial septation is the predominant human phenotype. Supporting Evidence: PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. |
| GO:0003281 ventricular septum development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ventricular septum development (mouse transfer). Reason: Supported by VSD in human GATA4 mutation carriers and DORV/CAVC in hypomorphic mice, but atrial septation is the predominant human phenotype. Supporting Evidence: PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. |
| GO:0003289 atrial septum primum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Atrial septum primum morphogenesis (mouse transfer). Reason: Consistent with GATA4's role in atrial septation and AV septal defects; a specific sub-process of atrial septum morphogenesis (GO:0060413), which is accepted. Supporting Evidence: PMID:12845333 These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 PMID:21330551 atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency |
| GO:0003289 atrial septum primum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrial septum primum morphogenesis (mouse transfer). Reason: Consistent with GATA4's role in atrial septation and AV septal defects; a specific sub-process of atrial septum morphogenesis (GO:0060413), which is accepted. Supporting Evidence: PMID:12845333 These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 PMID:21330551 atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency |
| GO:0003290 atrial septum secundum morphogenesis | IMP PMID:20347099 A novel mutation in GATA4 gene associated with dominant inhe... | KEEP AS NON CORE | Summary: IMP from a family with dominant inherited ASD carrying GATA4 M310V. Reason: Human genetic segregation supports a role in atrial septation; the abstract does not specify the ASD subtype or mechanism, so the secundum-specific term is retained as non-core, with the broader atrial septum morphogenesis accepted. Supporting Evidence: PMID:20347099 We identified a novel M310V mutation in GATA4 gene that is located in the NLS region and leads to hereditary ASD in a Chinese family |
| GO:0003677 DNA binding | IDA PMID:24000169 GATA4 loss-of-function mutations underlie familial tetralogy... | MODIFY | Summary: IDA (EMSA) of DNA binding for wild-type and TOF-associated GATA4 mutants. Reason: Correct but uninformative; GATA4 binds GATA motifs in Pol II cis-regulatory regions, so the specific term GO:0000978 is preferred. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Generic DNA binding (electronic / ortholog transfer). Reason: Under-specific; replace with RNA polymerase II cis-regulatory region sequence-specific DNA binding, which is directly supported for human GATA4. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | MODIFY | Summary: Generic DNA binding (electronic / ortholog transfer). Reason: Under-specific; replace with RNA polymerase II cis-regulatory region sequence-specific DNA binding, which is directly supported for human GATA4. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin binding (Ensembl Compara transfer). Reason: GATA-4 binds its sites within linker-histone-compacted nucleosome arrays and opens local chromatin without ATP-dependent remodelers, a pioneer-like property. Supporting Evidence: PMID:11864602 HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:9312027 The cardiac transcription factors Nkx2-5 and GATA-4 are mutu... | ACCEPT | Summary: IDA: GATA4 contributes to DNA-binding TF activity, synergizing with NKX2-5 on the ANF promoter. Reason: GATA4 and NKX2-5 act as mutual cofactors on the NPPA/ANF promoter. GATA4 also independently enables this activity, so the contributes_to statement is a correct, weaker claim. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to DNA-binding transcription factor activity. Reason: Correct parent of the core GO:0000981 activity. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0005515 protein binding | IPI PMID:10075728 Context-dependent transcriptional cooperation mediated by ca... | MODIFY | Summary: IPI with NKX2-5 (ANF promoter cooperation study). Reason: Generic 'protein binding' is uninformative. The partner, NKX2-5, is a Pol II DNA-binding TF that synergizes with GATA4 on the ANP promoter, so GO:0061629 is appropriate (consistent with the NKX2-5 reviews). Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:10075728 We also found that Csx/Nkx-2.5 and GATA-4 displayed synergistic transcriptional activation of the ANP promoter |
| GO:0005515 protein binding | IPI PMID:12845333 GATA4 mutations cause human congenital heart defects and rev... | MODIFY | Summary: IPI with TBX5; the G296S mutation abolishes the interaction. Reason: Generic 'protein binding' is uninformative. TBX5 is a T-box DNA-binding TF partner; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:12845333 the Gata4 mutation abrogated a physical interaction between Gata4 and TBX5 |
| GO:0005515 protein binding | IPI PMID:15485867 Hairy-related transcription factors inhibit GATA-dependent c... | MODIFY | Summary: IPI with Hairy-related (HRT/HEY) bHLH repressors. Reason: Generic 'protein binding' is uninformative. HRT/HEY proteins are DNA-binding bHLH transcription factors that bind GATA4 and inhibit its activity; GO:0061629 captures the interaction. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:15485867 HRT proteins physically interacted with GATA proteins, and the basic domain of HRT was critical for physical association as well as transcriptional inhibition |
| GO:0005515 protein binding | IPI PMID:15485867 Hairy-related transcription factors inhibit GATA-dependent c... | MODIFY | Summary: IPI with Hairy-related (HRT/HEY) bHLH repressors. Reason: Generic 'protein binding' is uninformative. HRT/HEY proteins are DNA-binding bHLH transcription factors that bind GATA4 and inhibit its activity; GO:0061629 captures the interaction. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:15485867 HRT proteins physically interacted with GATA proteins, and the basic domain of HRT was critical for physical association as well as transcriptional inhibition |
| GO:0005515 protein binding | IPI PMID:15485867 Hairy-related transcription factors inhibit GATA-dependent c... | MODIFY | Summary: IPI with Hairy-related (HRT/HEY) bHLH repressors. Reason: Generic 'protein binding' is uninformative. HRT/HEY proteins are DNA-binding bHLH transcription factors that bind GATA4 and inhibit its activity; GO:0061629 captures the interaction. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:15485867 HRT proteins physically interacted with GATA proteins, and the basic domain of HRT was critical for physical association as well as transcriptional inhibition |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: IPI with mouse Hey1/Hey2/HeyL bHLH repressors. Reason: Generic 'protein binding' is uninformative. Hey proteins are DNA-binding bHLH TFs that repress GATA4 by direct binding; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:16199874 Protein interaction and mutation analyses suggest that repression is due to direct binding of Hey proteins to GATA4 and GATA6, blocking their transcriptional activity |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: IPI with mouse Hey1/Hey2/HeyL bHLH repressors. Reason: Generic 'protein binding' is uninformative. Hey proteins are DNA-binding bHLH TFs that repress GATA4 by direct binding; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:16199874 Protein interaction and mutation analyses suggest that repression is due to direct binding of Hey proteins to GATA4 and GATA6, blocking their transcriptional activity |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: IPI with mouse Hey1/Hey2/HeyL bHLH repressors. Reason: Generic 'protein binding' is uninformative. Hey proteins are DNA-binding bHLH TFs that repress GATA4 by direct binding; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:16199874 Protein interaction and mutation analyses suggest that repression is due to direct binding of Hey proteins to GATA4 and GATA6, blocking their transcriptional activity |
| GO:0005515 protein binding | IPI PMID:17053787 The Kruppel-like transcription factor KLF13 is a novel regul... | MODIFY | Summary: IPI with the Kruppel-like factor KLF13. Reason: Generic 'protein binding' is uninformative. KLF13 is a DNA-binding zinc-finger TF that physically and functionally cooperates with GATA4; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:17053787 Physical and functional interaction with GATA-4, a dosage-sensitive cardiac regulator, provides a mechanistic explanation for KLF13 action |
| GO:0005515 protein binding | IPI PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | MODIFY | Summary: IPI (far-Western) with NR5A1/SF-1. Reason: Generic 'protein binding' is uninformative. NR5A1 is a nuclear receptor DNA-binding TF that synergizes with GATA4 on AMH; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:21220346 both the WT and mutant GATA4 proteins retained their ability to interact with NR5A1 |
| GO:0005515 protein binding | IPI PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | MODIFY | Summary: IPI (far-Western) with ZFPM2/FOG2, lost in the G221R N-terminal finger mutant. Reason: Generic 'protein binding' is uninformative. FOG2 is a non-DNA-binding multi-zinc-finger transcriptional cofactor of GATA factors, so transcription coregulator binding (GO:0001221) is the informative term. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:21220346 the mutant p.Gly221Arg GATA4 protein failed to interact with the FOG2 protein PMID:12223418 These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development. |
| GO:0005515 protein binding | IPI PMID:24000169 GATA4 loss-of-function mutations underlie familial tetralogy... | MODIFY | Summary: IPI with TBX5; the N285S mutation disrupts the interaction. Reason: Generic 'protein binding' is uninformative. TBX5 is a DNA-binding TF partner; replace with GO:0061629. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:24000169 the N285S mutation completely disrupted the physical interaction between GATA4 and TBX5 |
| GO:0005515 protein binding | IPI PMID:35182466 Transcription factor protein interactomes reveal genetic det... | MODIFY | Summary: IPI from an AP-MS interactome of cardiac TFs (BRD4, GLYR1, SMARCC1). Reason: Generic 'protein binding' is uninformative. The partners are chromatin-associated transcriptional coregulators (BET coactivator BRD4, GLYR1, BAF subunit SMARCC1); GO:0001221 transcription coregulator binding is the informative replacement. Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:35182466 BRD4 and SMARCC1, CHD candidate genes and GATA4 interactors |
| GO:0005515 protein binding | IPI PMID:9312027 The cardiac transcription factors Nkx2-5 and GATA-4 are mutu... | MODIFY | Summary: IPI with NKX2-5 mapping to the GATA4 C-terminal zinc finger. Reason: Generic 'protein binding' is uninformative. NKX2-5 is a homeodomain DNA-binding TF; replace with GO:0061629 (consistent with the NKX2-5 reviews). Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:9312027 The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005634 nucleus | IDA PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005634 nucleus | IDA PMID:24000169 GATA4 loss-of-function mutations underlie familial tetralogy... | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005634 nucleus | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005634 nucleus | NAS PMID:12845333 GATA4 mutations cause human congenital heart defects and rev... | ACCEPT | Summary: Nuclear localization. Reason: GATA4 is a nuclear transcription factor; GFP-tagged GATA4 shows strong nuclear localization. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleoplasm. Reason: Appropriate sub-nuclear location for a chromatin-bound transcription factor (Reactome: FOG/ZFPM proteins bind GATA proteins). Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-996755 | ACCEPT | Summary: Nucleoplasm. Reason: Appropriate sub-nuclear location for a chromatin-bound transcription factor (Reactome: FOG/ZFPM proteins bind GATA proteins). Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: Regulation of DNA-templated transcription. Reason: Correct but general; more specific positive regulation of transcription by RNA polymerase II is annotated with experimental support. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0006355 regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Regulation of DNA-templated transcription. Reason: Correct but general; more specific positive regulation of transcription by RNA polymerase II is annotated with experimental support. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II (InterPro). Reason: Correct; GATA4 regulates Pol II target genes. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0007267 cell-cell signaling | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Cell-cell signaling (ISS), inferred from mouse Gata4, where loss of the GATA4-FOG interaction disturbs epithelial-mesenchymal signalling in the developing stomach through altered Shh and Fgf10 expression (PMID:16127717). Reason: The row is inferred from mouse Gata4, annotated from a mutant phenotype: in mice expressing a GATA4 that cannot bind FOG cofactors, Sonic hedgehog is over-expressed in hindstomach epithelium and FGF10 falls in the adjacent mesenchyme, and the authors conclude that the GATA4-FOG interaction is required for proper epithelial-mesenchymal signalling (PMID:16127717). The claim therefore has an experimental basis. What the experiment shows is that GATA4 controls expression of signalling molecules; a nuclear transcription factor does not itself transmit signals between cells. The term over-reads the phenotype rather than being unsupported, so it is marked as an over-annotation instead of removed. Supporting Evidence: PMID:21220346 Both the WT and mutant GATA4 proteins (green), when expressed in human embryonic kidney HEK 293-T cells, showed strong nuclear localization |
| GO:0007492 endoderm development | TAS PMID:20347099 A novel mutation in GATA4 gene associated with dominant inhe... | KEEP AS NON CORE | Summary: TAS to endoderm development, citing a familial ASD paper. Reason: The cited paper is about ASD, but GATA4 does act in endoderm-derived tissues: Gata4-null embryos have foregut defects and liver bud/ventral pancreas development is disrupted. A real, non-cardiac developmental role. Supporting Evidence: PMID:9136932 This resulted in the defective formation of an organized foregut and anterior intestinal pore PMID:17451603 In the absence of GATA4, development of the liver and ventral pancreas was disrupted. |
| GO:0007507 heart development | IEA GO_REF:0000117 | ACCEPT | Summary: Heart development (ARBA). Reason: Core biological process; matches the module annoton (GO:0000981 in GO:0007507). Supporting Evidence: PMID:11297508 These findings establish an intrinsic requirement for GATA-4 in heart development. PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Zinc ion binding (InterPro). Reason: GATA4 has two GATA-type C4 zinc fingers; zinc binding is structural rather than functional. Supporting Evidence: PMID:21220346 The C-terminal zinc finger region is required for the recognition and binding of DNA, and the N-terminal zinc finger region contributes to the stability of this binding |
| GO:0008584 male gonad development | IEP PMID:17848411 Developmental changes in human fetal testicular cell numbers... | ACCEPT | Summary: IEP: GATA4 transcripts increase in human fetal testis during the second trimester. Reason: Expression data alone are weak evidence for process involvement, but the term itself is a core GATA4 role, well-supported by human loss-of-function and mouse genetics (see IMP annotation). Supporting Evidence: PMID:17848411 Expression of other transcripts known or postulated to be involved in testicular development (GATA4, GATA6, CXORF6, WNT2B, WNT4, WNT5A) increased significantly per testis during the second trimester |
| GO:0008584 male gonad development | IMP PMID:21220346 Loss-of-function mutation in GATA4 causes anomalies of human... | ACCEPT | Summary: IMP: human GATA4 G221R causes 46,XY DSD with defective AMH activation. Reason: GATA4 with its cofactor FOG2 and partner NR5A1 drives Sertoli-cell genes (SRY, SOX9, AMH); loss in humans causes testicular anomalies and in mice blocks testis differentiation. A second core developmental role. Supporting Evidence: PMID:21220346 Our data demonstrate the key role of GATA4 in human testicular development. PMID:12223418 These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development. |
| GO:0009410 response to xenobiotic stimulus | IMP PMID:20585342 Involvement of the atrial natriuretic peptide transcription ... | REMOVE | Summary: IMP to response to xenobiotic stimulus from an alcoholism pharmacogenetic association study. Reason: The study (abstract) reports a statistical association of an intronic GATA4 SNP with relapse during acamprosate treatment and with plasma ANP levels. A genetic association in patients does not show that the GATA4 product participates in a cellular response to a xenobiotic, and GATA4 has no known role in xenobiotic sensing/metabolism. Supporting Evidence: PMID:20585342 an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period |
| GO:0009612 response to mechanical stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to mechanical stimulus (Ensembl Compara from rodent). Reason: Derives from rodent pressure-overload hypertrophy studies in which GATA4 is a downstream transcriptional effector; 'response to' terms describe an indirect, context-specific effect rather than GATA4's function. |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | MODIFY | Summary: Anatomical structure morphogenesis (ARBA). Reason: Too general; the best-supported morphogenetic role is heart morphogenesis. Proposed replacements: heart morphogenesis Supporting Evidence: PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. |
| GO:0009888 tissue development | IEA GO_REF:0000117 | MODIFY | Summary: Tissue development (ARBA). Reason: Too general; replace with heart development, the primary tissue context. Proposed replacements: heart development Supporting Evidence: PMID:11297508 These findings establish an intrinsic requirement for GATA-4 in heart development. |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of autophagy (rodent transfer). Reason: Derived from rodent cardiomyocyte stress studies; an indirect transcriptional consequence rather than a function of GATA4, with no human evidence. |
| GO:0010575 positive regulation of vascular endothelial growth factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of VEGF production (rodent transfer). Reason: Mouse studies indicate myocardial GATA4 promotes cardiac angiogenesis through VEGF expression; plausible downstream transcriptional output, not core. Not independently verified here. |
| GO:0010575 positive regulation of vascular endothelial growth factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of VEGF production (rodent transfer). Reason: Mouse studies indicate myocardial GATA4 promotes cardiac angiogenesis through VEGF expression; plausible downstream transcriptional output, not core. Not independently verified here. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of gene expression. Reason: True but generic; covered by positive regulation of transcription by RNA polymerase II. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of gene expression. Reason: GATA4 with TBX5 represses non-cardiac genes in cardiomyocytes; generic, secondary. Supporting Evidence: PMID:27984724 the GATA4-G296S mutation led to failure of GATA4 and TBX5-mediated repression at non-cardiac genes |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle cell apoptotic process (rodent transfer). Reason: GATA4 is a positive regulator of postnatal cardiomyocyte survival in rodents; a downstream, context-dependent role. Supporting Evidence: PMID:17053787 GATA-4 is also an essential dosage-sensitive regulator of postnatal cardiomyocyte survival and homeostasis |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle cell apoptotic process (rodent transfer). Reason: GATA4 is a positive regulator of postnatal cardiomyocyte survival in rodents; a downstream, context-dependent role. Supporting Evidence: PMID:17053787 GATA-4 is also an essential dosage-sensitive regulator of postnatal cardiomyocyte survival and homeostasis |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear body (HPA immunofluorescence). Reason: Consistent with nuclear localization; sub-nuclear foci are not functionally characterized. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Protein kinase binding (rodent transfer). Reason: GATA4 is a substrate of kinases (e.g. MAPK, CDK9-containing complexes), but kinase binding is not an activity GATA4 performs for its function; uninformative. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | MODIFY | Summary: Cell differentiation (ARBA). Reason: Too general. GATA4 promotes cardiomyocyte differentiation in progenitor cultures, so cardiac muscle cell differentiation is the informative term. Proposed replacements: cardiac muscle cell differentiation Supporting Evidence: PMID:17053787 In vitro , cardiac progenitors lacking GATA-4 fail to upregulate Nkx2.5 and other regulators of cardiogenesis; they do not differentiate into cardiomyocytes and undergo apoptosis at an early stage |
| GO:0030513 positive regulation of BMP signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of BMP signaling pathway (rodent transfer). Reason: GATA4 is a transcriptional effector of BMP-induced cardiac gene expression and cooperates with SMAD4, but it does not regulate the BMP signal transduction pathway itself. Supporting Evidence: PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity |
| GO:0032526 response to retinoic acid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to retinoic acid / vitamin A (rat transfer). Reason: Expression-response observations in rodent tissues; not a function of GATA4. |
| GO:0033189 response to vitamin A | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to retinoic acid / vitamin A (rat transfer). Reason: Expression-response observations in rodent tissues; not a function of GATA4. |
| GO:0035054 embryonic heart tube anterior/posterior pattern specification | ISS GO_REF:0000024 | UNDECIDED | Summary: Embryonic heart tube anterior/posterior pattern specification (mouse transfer). Reason: Transferred from mouse Gata4 without a human-accessible primary reference in this review; GATA4 null embryos lack a fused heart tube, which complicates interpretation. Not verified. |
| GO:0036302 atrioventricular canal development | IEA GO_REF:0000107 | ACCEPT | Summary: Atrioventricular canal development. Reason: Myocardial Gata4 deletion and 70% GATA4 reduction cause AV canal defects (common AV canal); human mutations cause AVSD. Supporting Evidence: PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. |
| GO:0036302 atrioventricular canal development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | ACCEPT | Summary: Atrioventricular canal development. Reason: Myocardial Gata4 deletion and 70% GATA4 reduction cause AV canal defects (common AV canal); human mutations cause AVSD. Supporting Evidence: PMID:15464586 These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. |
| GO:0042060 wound healing | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Wound healing (mouse transfer). Reason: Probably reflects tissue-injury studies (e.g. cardiac or liver injury); indirect, and covered more precisely by cardiac muscle tissue regeneration. |
| GO:0042060 wound healing | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Wound healing (mouse transfer). Reason: Probably reflects tissue-injury studies (e.g. cardiac or liver injury); indirect, and covered more precisely by cardiac muscle tissue regeneration. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process. Reason: GATA4-deficient cardiac progenitors undergo apoptosis and GATA4 supports cardiomyocyte survival; a secondary consequence of its transcriptional program. Supporting Evidence: PMID:17053787 In vitro , cardiac progenitors lacking GATA-4 fail to upregulate Nkx2.5 and other regulators of cardiogenesis; they do not differentiate into cardiomyocytes and undergo apoptosis at an early stage |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Sequence-specific DNA binding. Reason: GATA4 binds the (A/T)GATA(A/G) motif via its C-terminal zinc finger. Supporting Evidence: PMID:21220346 The C-terminal zinc finger region is required for the recognition and binding of DNA, and the N-terminal zinc finger region contributes to the stability of this binding PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0043565 sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-specific DNA binding. Reason: GATA4 binds the (A/T)GATA(A/G) motif via its C-terminal zinc finger. Supporting Evidence: PMID:21220346 The C-terminal zinc finger region is required for the recognition and binding of DNA, and the N-terminal zinc finger region contributes to the stability of this binding PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0043565 sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-specific DNA binding. Reason: GATA4 binds the (A/T)GATA(A/G) motif via its C-terminal zinc finger. Supporting Evidence: PMID:21220346 The C-terminal zinc finger region is required for the recognition and binding of DNA, and the N-terminal zinc finger region contributes to the stability of this binding PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:0045165 cell fate commitment | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cell fate commitment (IBA, GATA family). Reason: GATA factors act in fate decisions across metazoa, but mouse Gata4 is not essential for cardiac lineage specification (likely redundancy with GATA5/6), so this is retained as non-core. Supporting Evidence: PMID:9136932 these results demonstrated that GATA4 is not essential for the specification of the cardiac cell lineages |
| GO:0045766 positive regulation of angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of angiogenesis (mouse transfer). Reason: Mouse cardiac GATA4 promotes myocardial capillary density via VEGF; downstream, non-core. |
| GO:0045766 positive regulation of angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of angiogenesis (mouse transfer). Reason: Mouse cardiac GATA4 promotes myocardial capillary density via VEGF; downstream, non-core. |
| GO:0045787 positive regulation of cell cycle | IEA GO_REF:0000107 | MODIFY | Summary: Positive regulation of cell cycle (rodent transfer). Reason: The supported role is promotion of cardiomyocyte proliferation: myocardial Gata4 deletion or hypomorphism reduces cardiomyocyte proliferation. Proposed replacements: positive regulation of cardiac muscle cell proliferation Supporting Evidence: PMID:15902305 Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. PMID:15464586 Myocardial hypoplasia was associated with diminished cardiomyocyte proliferation. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:24000169 GATA4 loss-of-function mutations underlie familial tetralogy... | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: GATA4 activates transcription of target genes; TOF mutants show reduced transcriptional activity. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: GATA4 activates transcription of target genes; TOF mutants show reduced transcriptional activity. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: GATA4 activates transcription of target genes; TOF mutants show reduced transcriptional activity. Supporting Evidence: PMID:24000169 the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: IDA: Gata4 and Smad4 cooperatively activate the Id2 promoter. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:29325903 GATA4 Loss-of-Function Mutation and the Congenitally Bicuspi... | ACCEPT | Summary: IDA: GATA4 transactivation lost in the BAV E147X mutant, which also loses synergy with NKX2-5. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS PMID:12845333 GATA4 mutations cause human congenital heart defects and rev... | ACCEPT | Summary: ISS citing the GATA4-TBX5 interaction paper. Reason: Core process: GATA4 activates Pol II genes (NPPA, AMH, Id2), alone and synergistically with NKX2-5, TBX5, SMAD4 and NR5A1. Supporting Evidence: PMID:9312027 Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity PMID:29325903 Functional deciphers revealed that the mutant GATA4 protein lost transcriptional activity compared with its wild-type counterpart |
| GO:0048617 embryonic foregut morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Embryonic foregut morphogenesis (mouse transfer). Reason: Gata4-null embryos fail to form an organized foregut; a real endodermal developmental role, partly due to the extraembryonic/ventral folding defect. Supporting Evidence: PMID:9136932 This resulted in the defective formation of an organized foregut and anterior intestinal pore PMID:9136933 Mutant embryos most notably lacked a primitive heart tube and foregut |
| GO:0051525 NFAT protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: NFAT protein binding (rodent transfer). Reason: GATA4 binds NFATC4 via its second zinc finger (UniProt, by similarity) in calcineurin-dependent hypertrophic gene expression; a real but context-specific partner interaction. |
| GO:0055007 cardiac muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiac muscle cell differentiation (rodent transfer). Reason: GATA4 promotes cardiomyocyte differentiation in progenitor cultures, but in vivo Gata4-null cardiomyocytes still differentiate, reflecting redundancy; retained as non-core. Supporting Evidence: PMID:17053787 In vitro , cardiac progenitors lacking GATA-4 fail to upregulate Nkx2.5 and other regulators of cardiogenesis; they do not differentiate into cardiomyocytes and undergo apoptosis at an early stage PMID:9136932 these results demonstrated that GATA4 is not essential for the specification of the cardiac cell lineages |
| GO:0060290 transdifferentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transdifferentiation (rodent transfer). Reason: Reflects forced-expression reprogramming of fibroblasts to cardiomyocyte-like cells (GATA4 with MEF2C/TBX5); an experimental manipulation rather than a physiological process. |
| GO:0060413 atrial septum morphogenesis | IMP PMID:12845333 GATA4 mutations cause human congenital heart defects and rev... | ACCEPT | Summary: IMP: GATA4 G296S/E359del mutations segregate with cardiac septal defects. Reason: Atrial septal defect is the hallmark human GATA4 phenotype; the mutation impairs DNA binding and TBX5 interaction. Supporting Evidence: PMID:12845333 These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 PMID:12845333 This mutation resulted in diminished DNA-binding affinity and transcriptional activity of Gata4 |
| GO:0060575 intestinal epithelial cell differentiation | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | KEEP AS NON CORE | Summary: IDA: GATA-4 activates the IFABP promoter and is expressed toward the villus tip. Reason: Supports a role of GATA4 in activating terminal-differentiation genes in intestinal epithelium; non-cardiac, non-core. Supporting Evidence: PMID:9566909 GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP |
| GO:0061026 cardiac muscle tissue regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiac muscle tissue regeneration (mouse transfer). Reason: GATA4 is required for regenerative cardiomyocyte proliferation in model organisms; consistent with its pro-proliferative role but not verified here. |
| GO:0061026 cardiac muscle tissue regeneration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiac muscle tissue regeneration (mouse transfer). Reason: GATA4 is required for regenerative cardiomyocyte proliferation in model organisms; consistent with its pro-proliferative role but not verified here. |
| GO:0061049 cell growth involved in cardiac muscle cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell growth involved in cardiac muscle cell development (rodent transfer). Reason: GATA4 is a transcriptional mediator of cardiomyocyte hypertrophic growth (UniProt: promotes cardiac myocyte enlargement); non-core. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding. Reason: Core: GATA4 forms cooperative complexes with partner DNA-binding TFs (NKX2-5, TBX5, SMAD4, NR5A1) through its zinc fingers to activate cardiac and gonadal genes. Supporting Evidence: PMID:9312027 The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension PMID:12845333 the Gata4 mutation abrogated a physical interaction between Gata4 and TBX5 |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: IPI: SMAD4 pulls down GATA4; GATA4 AVSD mutants bind SMAD4 poorly. Reason: Core: GATA4 forms cooperative complexes with partner DNA-binding TFs (NKX2-5, TBX5, SMAD4, NR5A1) through its zinc fingers to activate cardiac and gonadal genes. Supporting Evidence: PMID:21330551 SMAD4 efficiently precipitated wild-type GATA4 |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:9858576 Identification of the in vivo casein kinase II phosphorylati... | ACCEPT | Summary: IPI: GST-GATA4 pull-down of Csx/Nkx2.5. Reason: Core: GATA4 forms cooperative complexes with partner DNA-binding TFs (NKX2-5, TBX5, SMAD4, NR5A1) through its zinc fingers to activate cardiac and gonadal genes. Supporting Evidence: PMID:9858576 Although the mutation in the CKII site did not affect GATA4-Csx/Nkx2.5 interaction in vitro |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | ISS GO_REF:0000024 | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding. Reason: Core: GATA4 forms cooperative complexes with partner DNA-binding TFs (NKX2-5, TBX5, SMAD4, NR5A1) through its zinc fingers to activate cardiac and gonadal genes. Supporting Evidence: PMID:9312027 The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension PMID:12845333 the Gata4 mutation abrogated a physical interaction between Gata4 and TBX5 |
| GO:0070410 co-SMAD binding | IPI PMID:21330551 Transcription factor genes Smad4 and Gata4 cooperatively reg... | ACCEPT | Summary: IPI: co-SMAD binding (SMAD4). Reason: SMAD4 binds the GATA4 C-terminal zinc finger region and the two cooperatively activate Id2 in endocardial cushions; disrupted by AVSD-causing GATA4 mutations. Supporting Evidence: PMID:21330551 SMAD4 efficiently precipitated wild-type GATA4 PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity |
| GO:0071333 cellular response to glucose stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to glucose stimulus (rodent transfer). Reason: Expression-response observation; not a function of GATA4. |
| GO:0086004 regulation of cardiac muscle cell contraction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of cardiac muscle cell contraction (rodent transfer). Reason: GATA4 G296S iPSC-cardiomyocytes show impaired contractility, but this is a downstream consequence of altered cardiac gene expression, not direct regulation of contraction. Supporting Evidence: PMID:27984724 iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:9312027 The cardiac transcription factors Nkx2-5 and GATA-4 are mutu... | ACCEPT | Summary: IDA: GATA4 forms a transcription regulator complex with NKX2-5. Reason: GATA4 and NKX2-5 physically associate and synergistically activate ANF; GATA4 also forms complexes with TBX5 and SMAD4. Supporting Evidence: PMID:9312027 The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: DNA-binding transcription factor binding (rodent transfer). Reason: Correct parent of GO:0061629, which is supported by direct human/mouse data. Supporting Evidence: PMID:9312027 The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension |
| GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of oxidative stress-induced intrinsic apoptotic signaling (mouse transfer). Reason: Context-specific cardioprotective output of GATA4 transcription in rodent models; non-core. |
| GO:1902895 positive regulation of miRNA transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of miRNA transcription (rodent transfer). Reason: GATA4 as a Pol II TF can activate miRNA host genes; plausible but not verified here. |
| GO:1905204 negative regulation of connective tissue replacement | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of connective tissue replacement (rodent transfer). Reason: Likely from cardiac/liver fibrosis models; an indirect tissue-level outcome rather than a function of GATA4. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: IDA from a high-throughput methyl-SELEX study of human TF binding specificities. Reason: GATA4 is not named in the cached main text (data are in supplementary tables), but sequence-specific double-stranded DNA binding is well established for GATA4 (EMSA, ChIP), so the curator's annotation is retained. Supporting Evidence: PMID:21220346 we performed EMSA, which showed WT GATA4 binding to the GATA4-responsive element on the AMH promoter |
| GO:2001234 negative regulation of apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic signaling pathway. Reason: Cardiomyocyte survival role; downstream of transcriptional activity, non-core. Supporting Evidence: PMID:17053787 GATA-4 is also an essential dosage-sensitive regulator of postnatal cardiomyocyte survival and homeostasis |
| GO:2001234 negative regulation of apoptotic signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic signaling pathway. Reason: Cardiomyocyte survival role; downstream of transcriptional activity, non-core. Supporting Evidence: PMID:17053787 GATA-4 is also an essential dosage-sensitive regulator of postnatal cardiomyocyte survival and homeostasis |
Loading supporting content…
Download this section (compressed HTML)Q: Which cardiac and endodermal GATA4 functions are masked by redundancy with GATA5 and GATA6, given that Gata4-null cardiomyocytes still differentiate?
Q: Does GATA4 act as a bona fide pioneer factor at cardiac enhancers in vivo (as it does on compacted albumin-enhancer chromatin in vitro), and is TBX5 recruitment dependent on prior GATA4-driven opening?
Q: Should GATA4's FOG2-dependent repressive activity on some promoters be captured with a context-specific transcription repressor annotation in human?
Experiment: Time-resolved ATAC-seq and CUT&RUN for GATA4, TBX5 and NKX2-5 during human iPSC cardiac differentiation using degron-tagged GATA4 to test acute loss of accessibility.
Hypothesis: GATA4 opens chromatin at a subset of cardiac enhancers before TBX5/NKX2-5 binding.
Type: genome-wide chromatin accessibility and occupancy profiling
Experiment: Systematically profile FOG2, NR5A1, TBX5, NKX2-5 and SMAD4 binding and reporter synergy for a panel of patient GATA4 variants.
Hypothesis: Gonad-restricted DSD mutations (e.g. G221R) differ from cardiac-only mutations by disrupting FOG2 binding rather than partner-TF synergy.
Type: variant functional characterization
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)