GATA-4, -5, and -6 are zinc finger-containing transcription factors that regulate tissue-specific gene expression in vertebrates. These factors contain a highly conserved DNA-binding domain with two zinc fingers, and they are divided into two subfamilies based on expression patterns. GATA-1, -2, and -3 are expressed in hematopoietic cells, while GATA-4, -5, and -6 are expressed in mesoderm and endoderm-derived tissues, including the heart, liver, lung, gonad, and gut. Targeted disruption of these genes in mice has revealed their roles in heart, endoderm, lung epithelium, and genitourinary tract development. GATA-4, -5, and -6 proteins are structurally similar, with high sequence identity in their DNA-binding regions. Structural and mutagenesis studies suggest that the C-terminal zinc finger and adjacent basic domain are essential for DNA binding. These factors also have nuclear localization sequences and transcriptional activation domains, with some conservation among GATA-4, -5, and -6. GATA-4, -5, and -6 bind to GATA or GATA-like DNA sequences, and their binding preferences may vary based on flanking nucleotides or cofactors, leading to tissue-specific gene regulation. GATA-4 is critical for heart development, with GATA-4 null mice dying due to heart defects. GATA-5 is involved in genitourinary tract development, while GATA-6 is essential for visceral endoderm function. GATA-4 and -6 are interdependent, with each regulating the other's expression. GATA-4, -5, and -6 regulate gene expression in the heart, liver, lung, and gut, and are involved in cardiac hypertrophy and other developmental processes. These factors interact with other transcription factors, such as Nkx2.5, NFATc4, and MEF-2, to regulate gene expression. GATA-4 also interacts with p300/CBP and FOG-2, which may influence its transcriptional activity. GATA-4, -5, and -6 are important regulators of tissue-specific gene expression in multiple endoderm and mesoderm-derived tissues, and their functions are likely mediated through interactions with other semi-restricted transcription factors. Overall, GATA-4, -5, and -6 play critical roles in regulating gene expression in various tissues, contributing to development and disease.GATA-4, -5, and -6 are zinc finger-containing transcription factors that regulate tissue-specific gene expression in vertebrates. These factors contain a highly conserved DNA-binding domain with two zinc fingers, and they are divided into two subfamilies based on expression patterns. GATA-1, -2, and -3 are expressed in hematopoietic cells, while GATA-4, -5, and -6 are expressed in mesoderm and endoderm-derived tissues, including the heart, liver, lung, gonad, and gut. Targeted disruption of these genes in mice has revealed their roles in heart, endoderm, lung epithelium, and genitourinary tract development. GATA-4, -5, and -6 proteins are structurally similar, with high sequence identity in their DNA-binding regions. Structural and mutagenesis studies suggest that the C-terminal zinc finger and adjacent basic domain are essential for DNA binding. These factors also have nuclear localization sequences and transcriptional activation domains, with some conservation among GATA-4, -5, and -6. GATA-4, -5, and -6 bind to GATA or GATA-like DNA sequences, and their binding preferences may vary based on flanking nucleotides or cofactors, leading to tissue-specific gene regulation. GATA-4 is critical for heart development, with GATA-4 null mice dying due to heart defects. GATA-5 is involved in genitourinary tract development, while GATA-6 is essential for visceral endoderm function. GATA-4 and -6 are interdependent, with each regulating the other's expression. GATA-4, -5, and -6 regulate gene expression in the heart, liver, lung, and gut, and are involved in cardiac hypertrophy and other developmental processes. These factors interact with other transcription factors, such as Nkx2.5, NFATc4, and MEF-2, to regulate gene expression. GATA-4 also interacts with p300/CBP and FOG-2, which may influence its transcriptional activity. GATA-4, -5, and -6 are important regulators of tissue-specific gene expression in multiple endoderm and mesoderm-derived tissues, and their functions are likely mediated through interactions with other semi-restricted transcription factors. Overall, GATA-4, -5, and -6 play critical roles in regulating gene expression in various tissues, contributing to development and disease.