Targeting the WNT pathway using epigenetic inhibitors. WNT signaling culminates when, upon recruitment of β-catenin/CBP or β-catenin/p300 complexes to the DNA via a TCF/LEF family member, CBP and p300 activate transcription by acetylating histone H3. (A) Treatment with ICG-001 disrupts the interaction of CBP with β-catenin, blocking CBP-driven, but not p300-driven transcription. (B) In contrast to the effects of ICG-001, C646 competes with acetyl-coA for the Lys-coA binding pocket of both CBP and p300, preventing HAT activity of both complexes. (C) Examples of predicted gene expression differences mediated by β-catenin/CBP vs. β-catenin/p300 complexes . (D) RNA levels in HCT116 and PANC1 cells of the various components of the WNT signaling model.