Growth and development require a strict control of the process of gene expression. Abnormalities in transcription have been linked to a variety of human diseases, including birth defects and neoplasia. Our studies focus on the GATA transcription factors which are zinc finger proteins that recognize a consensus DNA sequence (A/T)GATA(A/G), known as GATA-motif, an essential cis -acting element in the promoters and the enhancers of a variety of genes. These proteins form two subgroups based on their sequence homology and expression patterns. The first subgroup, which consists of GATA-1, -2, and -3, is essential for normal hematopoiesis. The second subgroup members, namely GATA-4, -5, and -6, are expressed in the heart, gut epithelium, yolk sac endoderm, and several endocrine organs. The specificity of gene regulation by GATA factors is partly achieved by cofactors that act in concert with them. Two related factors, FOG-1 and FOG-2 (FOG for friend-of-GATA), bind to one of the two zinc fingers of the GATA proteins to activate or repress the gene transactivation by the GATA proteins. The essential role of GATA factors in the development of the endocrine- and the endoderm-derived organs has begun to unravel during the past years, but their ultimate target genes and their role in human endocrine and endoderm disease and cancer have still remained largely unknown. The long-term goal of our projects is to recognize potential targets for future diagnostics and therapy.