title: Wnt/β-catenin-dependent acetylation of Pygo2 by CBP/p300 histone acetyltransferase family members.
abstract: 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 the present 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 HAT 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 the 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. Taken 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 away from the complex subsequent to target gene activation.
authors.affiliation: Terry Fox Cancer Research Labs, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada A1B 3V6.
authors.forename: Phillip G P
authors.initials: PG
authors.lastname: Andrews
authors.affiliation: Terry Fox Cancer Research Labs, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada A1B 3V6.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Kao
mesh_terms: D000107:Acetylation; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D047908:Intracellular Signaling Peptides and Proteins; C453401:PYGO2 protein, human; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D050880:p300-CBP Transcription Factors
keywords: Pygopus; chromatin remodeling; histone acetyltransferase; β-catenin