FIG. 11.

Model for Notch activation of CBF1-repressed promoters. CBF1 binds promoters carrying the sequence GTGGGAA. SKIP interacts with CBF1. SMRT contacts both SKIP and CBF1. SMRT is linked to a corepressor complex that includes Sin3A, SAP30, CIR, HDAC1, and HDAC2 (25, 28) and mediates promoter repression through chromatin remodeling. NotchIC competes with SMRT for contacts on both CBF1 and SKIP. Displacement of the corepressor complex relieves repression, and the promoter is further activated through the endogenous NotchIC transcriptional ACT. Loss of CBF1 interaction through mutation of the RAM domain or loss of interaction with SKIP through mutation of the fourth ankyrin repeat cripples the ability of NotchIC to activate CBF1-repressed promoters.