GATA4

Description

The GATA4 (GATA binding protein 4) is a protein-coding gene located on chromosome 8.

GATA4 is a transcription factor that belongs to the GATA family of zinc finger transcription factors. It recognizes the GATA motif, which is present in the promoters of many genes. GATA4 is thought to regulate genes involved in embryogenesis, myocardial differentiation, and function. Mutations in GATA4 have been linked to cardiac septal defects and reproductive defects. GATA4 is a critical transcription factor for proper mammalian cardiac development and essential for embryonic survival. It works in combination with other essential cardiac transcription factors like Nkx2-5 and Tbx5. GATA4 is expressed in both embryo and adult cardiomyocytes, functioning as a transcriptional regulator for numerous cardiac genes and regulating hypertrophic growth of the heart. It promotes cardiac morphogenesis, cardiomyocyte survival, and maintains cardiac function in the adult heart. Mutations or defects in the GATA4 gene can lead to a variety of cardiac problems including congenital heart disease, abnormal ventral folding, defects in the cardiac septum separating the atria and ventricles, and hypoplasia of the ventricular myocardium.

GATA4 is a transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a critical role in cardiac development and function. In collaboration with TBX5, it binds to cardiac super-enhancers, promoting cardiomyocyte gene expression while downregulating endocardial and endothelial gene expression. It is involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression, binding to BMP response element (BMPRE) DNA sequences within cardiac activating regions. GATA4 acts as a transcriptional activator of ANF in cooperation with NKX2-5, promoting cardiac myocyte enlargement. It is required during testicular development and may play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate lyase.

GATA4 is also known as ASD2, TACHD, TOF, VSD1.

Associated Diseases

• Testicular anomalies with or without congenital heart disease
• Atrial septal defect 2
• Familial atrial fibrillation
• Atrioventricular septal defect 4
• Ventricular septal defect 1
• 8p23.1 microdeletion syndrome
• Atrial septal defect, ostium secundum type
• Tetralogy of Fallot
• 46,XY partial gonadal dysgenesis