The minimal functional NOTCH coactivator complex that activates transcription from NOTCH regulatory elements is a heterotrimer composed of MAML (mastermind-like), NICD (NOTCH intracellular domain) and RBPJ (CSL) (Fryer et al. 2002). Structural studies indicate that NOTCH:RBPJ complexes can be pre-assembled on promoters of NOTCH-target genes and that MAML binds to a composite groove created by RBPJ and the NOTCH ankyrin domain (Nam et al. 2006). MAML is able to interact directly with a histone acetyltransferases EP300 (p300) and CREBBP. The presence of EP300 strongly activates NOTCH1 coactivator complex-mediated transcription and this positive effect is blocked by Lys-CoA, a selective inhibitor of EP300 histone acetyltransferase activity (Fryer et al. 2002). NICD1:RBPJ:MAML-mediated transcription increases threefold in the presence of both EP300 and PCAF, in comparison with the presence of EP300 alone (Wallberg et al. 2002).