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FLASH GENE
Symbol GATA4 contributors: mct - updated : 04-01-2016
HGNC name GATA binding protein 4
HGNC id 4173
Corresponding disease
ASD2 atrial septal defect 2
AVSD4 atrioventricular septal defect 4
CMD1NN Cardiomyopathy, dilated, 1NN
DEL8P23 chromosome 8p23.1 deletion
DIH2 congenital diaphragmatic hernia and 8p23.1 deletion
DUP8P23 chromosome 8p23.1 duplication
Location 8p23.1      Physical location : 11.561.716 - 11.617.509
Synonym name transcription factor GATA-4
Synonym symbol(s) MGC126629
DNA
TYPE functioning gene
STRUCTURE 55.79 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 3419 - 442 - 1995 7791790
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveintestinesmall intestine  highly
Endocrineadrenal glandcortex   
 pancreas   highly
Reproductiveovary   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousglia
Nervousneuron
ReproductiveSertoli cell
Skeletonosteoblast Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal
Text
  • yolk sac endoderm, heart formation
  • strongly expressed in the somatic cell population of the developing gonad before and during the time of sex determination
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two adjacent zinc finger motif of a distinctive form CXNCX(17)CNXC, associated basic domains
  • a stretch of alanine residues
  • two transcriptional activation domains
  • C terminal nuclear localization signal (NLS)
  • HOMOLOGY
    interspecies homolog to murine Gata4
    Homologene
    FAMILY
  • GATA zinc finger transcription factor family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • involved in lineage determination
  • regulating genes involved in embryogenesis and in myocardial differentiation and function, essential for functional separation of the four cardiac chambers)
  • required during early cardiac development and essential factor for generation of the proepicardium
  • important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress, and protects the heart from load-induced failure
  • potential tumor suppressor
  • having a role in the transcriptional regulation of the IL5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed
  • positively regulates cardiac BCL2 gene expression
  • potentially controling cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes (
  • required for cyclin D2, cyclin A2, and Cdk4 expression in the right ventricle and Cyclin D2 and Cdk4 promoters are bound and activated by GATA4 via multiple consensus GATA binding sites in each gene proximal promoter (
  • GATA4/5 exhibit tumor suppressive effects in colorectal cancer cells
  • transcriptional inducer of CDKN2B, leading to the attenuation of cyclin D1
  • negative regulator of astrocyte proliferation and growth
  • in collaboration with NKX2-5, nuclear translocation in tissue-specific mesenchymal stem cells drives cardiac differentiation
  • repressor role on ERBB2 gene expression plays a role in breast cancer
  • essential for ventral body plan and formation of linear heart tube
  • role for ZNF260 and GATA4 as mutual coactivators of a genetic program underlying cardiac hypertrophy
  • key role of GATA4 in human testicular development
  • GATA4 and SMAD4 cooperatively activated the ID2 promoter
  • GATA4, GATA45, GATA6 are indispensable for the lineage-specific development and differentiation of cells of endodermal and mesodermal origin
  • GATA4 and GATA6 are needed for normal ovarian function
  • novel role for GATA4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with SIRT1
  • negative effect of GATA4 in the reprogramming of somatic cells and potential role of GATA factors in the transcriptional networks that control cell lineage choices in the early embryo
  • transcription factors NKX2-5 and GATA4 cooperatively regulate cardiac-specific expression of LRRC10
  • essential role of the GATA4 protein in the ovarian morphogenetic program
  • acting as a negative regulator in osteoblast differentiation by downregulation of RUNX2
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to GATA sequence
    RNA
    small molecule
    protein
  • ZFPM2 (FOG2) (ZFPM2 in the early pulmonary mesenchyme participate in patterning the secondary bronchus of the accessory lobe)
  • TBX5
  • LHX9 gene represents the first direct target of the GATA4/ZFPM2 repressor complex in cardiac development
  • cardiac expression of TNNT1 strictly depends on the physical interaction between GATA4-ZFPM2 in the myocardium of both atria and ventricles
  • GATA4 may alter the activity of ZFPM2 by influencing its SUMOylation status
  • GSN induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation
  • Cyclin D2 and CDK4 as direct transcriptional targets of GATA4
  • cooperatively interacts with several proteins, including NR5A1 and FOG2, to regulate the expression of the sex-determining genes SRY (encoding sex-determining region Y), SOX9 (encoding SRY box 9), AMH (encoding anti-Müllerian hormone)
  • binding of the N-terminal portion of SMAD4 to the second zinc-finger domain of GATA4 (genetically cooperate in the endocardium during atrioventricular valve formation)
  • GATA5 interacts with GATA4 and GATA6 in outflow tract development
  • PTK2 inhibition resulted in the loss of the GATA4 transcription factor required for TNF-induced VCAM1 production
  • role for CCND2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival
  • LRRC10 is a transcriptional target of NKX2-5 and GATA4
  • sex determination requires interaction between the transcription factor GATA4 and its cofactor ZFPM2
  • interacted with DLX5 and subsequently decreased DLX5 binding activity to RUNX2 promoter region
  • NR4A1 functionally interacts with NFATC3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy
  • ZFPM2 is a multi-zinc finger protein that binds the transcriptional activator GATA4 and modulates GATA4-mediated regulation of target genes during heart development
  • GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells
  • cell & other
    REGULATION
    induced by TGFbeta, leading to the inhibition of astrocyte proliferation (Agnihotri 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL8P23 , DUP8P23 , ASD2 , CMD1NN , DIH2 , AVSD4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal adenocarcinoma
    constitutional germinal mutation      
    in congenital heart defects(ASD, VSD)
    constitutional     --low  
    in heart failure, with mild baseline systolic and diastolic dysfunction
    tumoral     --low  
    in ovarian and gastric cancer
    tumoral        
    no expression in malignant astrocytoma cell lines
    constitutional     --over  
    enhanced expression in inflammatory Bowel disease
    tumoral       loss of function
    epigenetic inactivation by methylation of CpG islands is an early frequent event during gastric carcinogenesis significantly correlated with H. pylori infection
    constitutional germinal mutation      
    heterozygous missence mutation in a family with 46,XY DSD (disorder of sex development) and congenital heart disease (
    constitutional   deletion    
    in congenital heart disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene for heart defects in del 8p23 ;
    for isolated congenital diaphragmatic hernia, ;
    Marker GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection
    Therapy target
    ANIMAL & CELL MODELS
  • Gata4(+/-)Gata5(+/-) mutant embryos have double outlet right ventricles (DORV), large ventricular septal defects (VSD) as well as hypertrophied mitral and tricuspid valves and aortic stenosis
  • simultaneous deletion of both murine Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis