Pygopus 2 (Pygo2) is a chromatin effector that plays an essential role in canonical Wnt signaling associated with development and stem cell growth. Its function is to facilitate histone acetylation by recruitment of histone acetyltransferases (HATs) at active sites of β-catenin-mediated transcription. In this study, we report that Pygo2 itself, is transiently acetylated when bound to the activated TCF/β-catenin transcription complex, which correlated with β-catenin binding and Axin2 gene activation. The HATs CBP/p300, but not GCN5/PCAF targeted specific Lysine residues of the N-terminal homology domain of Pygo2 for acetylation. Functional analyses revealed that the presence of CBP and p300 increased association of Pygo2 with GCN5, independent of Pygo2 acetylation status. Finally, while acetylation of Pygo2 had little effect on active β-catenin complex formation, p300 mediated Pygo2 acetylation resulted in the displacement of Pygo2 from the nucleus to the cytoplasm by targeting specific Lysine residues in the Pygo2 nuclear localization sequence. Together, these findings are consistent with a model in which acetylation of Pygo2 by CBP/p300 family members in the active TCF/β-catenin complex occurs coincident with histone acetylation and may be required for the recycling of Pygo2 complexes away from the complex subsequent to target gene activation.
- Chromatin remodeling
- histone acetyltransferase
- ©2016 The Author(s)
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