Requirement of two NFATc4 transactivation domains for CBP potentiation

Recruitment of the coactivator CREB-binding protein (CBP) to transcription factors is important for gene expression. Various regions of CBP such as th e KIX and CH3 domains have been shown to interact with numerous transcripti on factors. The NFAT group of transcription factors is involved in multiple biological processes. NFATc4/NFAT3 has been proposed to play an important role in heart hypertrophy, adipocyte differentiation, and learning and memo ry. We demonstrate here that two transactivation domains, located at the NH , and COOH termini of NFATc4, are critical for interacting with CBP. Each t ransactivation domain interacts with a distinct region of the CBP protein ( the KIX and CH3 domains). Binding of CBP potentiates NFATc4-mediated transc ription activity. Both transactivation domains of NFATc4 are required for C BP function. Removal of either NFATc4 transactivation domain abolishes CBP potentiation. Conversely, mutation of the KIX or CH3 domain prevents CBP-me diated potentiation of NFATc4 transcription activation. These data demonstr ate that formation of a functional NFATc4-CBP transcription complex require s interactions at two distinct sites.