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).
Fryer, CJ, Lamar, E, Jones, KA, Kintner, C, Turbachova, I
Lendahl, U, Wallberg, AE, Pedersen, K, Roeder, RG
Blacklow, SC, Nam, Y, Aster, JC, Song, L, Sliz, P
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