The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates.
Wnt growth factors regulate a variety of developmental processes by altering specific gene expression patterns. In vertebrates beta-catenin acts as transcriptional activator, which is needed to overcome target gene repression by Groucho/TLE proteins, and to permit promoter activation as the final consequence of Wnt signaling. However, the molecular mechanisms of transcriptional activation by beta-catenin are only poorly understood. Here we demonstrate that the closely related acetyltransferases p300 and CBP potentiate beta-catenin-mediated activation of the siamois promoter, a known Wnt target. beta-catenin and p300 also synergize to stimulate a synthetic reporter gene construct, whereas activation of the cyclin D1 promoter by beta-catenin is refractory to p300 stimulation. Axis formation and activation of the beta-catenin target genes siamois and Xnr-3 in Xenopus embryos are sensitive to the E1A oncoprotein, a known inhibitor of p300/CBP. The C-terminus of beta-catenin interacts directly with a region overlapping the CH-3 domain of p300. p300 could participate in alleviating promoter repression imposed by chromatin structure and in recruiting the basal transcription machinery to promoters of particular Wnt target genes.
Hecht
A
A
Max-Planck-Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany. hecht@immunbio.mpg.de
Vleminckx
K
K
Stemmler
M P
MP
van Roy
F
F
Kemler
R
R
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014162:Transfection; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D002843:Chromatin; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D005982:Glutathione Transferase