Transcription Cooperation by NFAT.C/EBP Composite Enhancer Complex

The nuclear factor of activated T cells (NFAT) group of transcription factors regulates gene expression in immune and non-immune cells. NFAT-mediated gene transcription is orchestrated, in part, by formation of a composite regulatory element. Here we demonstrate that NFAT interacts with transcription factor CCAAT/enhancer-binding protein (C/EBP) to form a composite enhancer complex, to potentiate expression of the peroxisome proliferator-activated receptor-gamma2 gene. Formation of a ternary NFAT.C/EBP.DNA complex is required for the transcriptional cooperation. A similar NFAT.C/EBP composite element is found in the regulatory region of the insulin-like growth factor 2, angiotensin-converting enzyme homolog, and transcription factor POU4F3 genes. Thus, the NFAT.C/EBP composite element represents a novel regulatory enhancer to direct NFAT-mediated gene transcription.