Functional interplay between CBP and PCAF in acetylation and regulation of transcription factor KLF13 activity.
The transcriptional co-activators CBP/p300 and PCAF participate in transcriptional activation by many factors. We have shown that both CBP/p300 and PCAF stimulate the transcriptional activation by KLF13, a member of the KLF/Sp1 family, either individually or cooperatively. Here we further investigated how CBP and PCAF acetylation regulate KLF13 activity, and ... how these two co-activators functionally interplay in the regulation of KLF13 activity. We found that CBP and PCAF acetylated KLF13 at specific lysine residues in the zinc finger domain of KLF13. The acetylation by CBP, however, resulted in disruption of KLF13 DNA binding. Although the acetyltransferase activity of CBP is not required for stimulating the DNA binding activity of all of the transcription factors that we have examined, the disruption of factor DNA binding by CBP acetylation is factor-specific. We further showed that PCAF and CBP act synergistically and antagonistically to regulate KLF13 DNA binding depending on the status of acetylation. PCAF blocked CBP acetylation and disruption of KLF13 DNA binding. Conversely, acetylation of KLF13 by CBP prevented PCAF stimulation of KLF13 DNA binding. PCAF blocked CBP disruption of KLF13 DNA binding by preventing CBP acetylation of KLF13. These results demonstrate that acetylation by CBP has distinct effects on transcription factor DNA binding, and that CBP and PCAF regulate each other functionally in their regulation of transcription factor DNA binding.
Mesh Terms:
Acetylation, Acetyltransferases, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, DNA, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Glutathione Transferase, Histone Acetyltransferases, Luciferases, Lysine, Molecular Sequence Data, Nuclear Proteins, Plasmids, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Acetylation, Acetyltransferases, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, DNA, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Glutathione Transferase, Histone Acetyltransferases, Luciferases, Lysine, Molecular Sequence Data, Nuclear Proteins, Plasmids, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
J. Mol. Biol.
Date: May. 30, 2003
PubMed ID: 12758070
View in: Pubmed Google Scholar
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