Functional Interaction between Coactivators CBP/p300, PCAF, and Transcription Factor FKLF2

Abstract

The Sp1/KLF family of factors regulates diverse cellular processes, including growth and development. Fetal Krüppel-like factor (FKLF2) is a new member of this family. In this study, we characterized the coactivators involved in FKLF2 transcriptional activation. Our results show that both CBP/p300 and p300/CBP-associated factor (PCAF) enhance FKLF2 transcriptional activity. We demonstrate that the acetyltransferase activity of PCAF but not that of CBP/p300 is required for stimulating FKLF2 transcription activity. We further show that p300 and PCAF act cooperatively in stimulating FKLF2 transcriptional activation. FKLF2 interacts with both CBP and PCAF through specific domains, and CBP and PCAF acetylate FKLF2. Both CBP/p300 and PCAF stimulate FKLF2 DNA binding activity. The integrity of the acetyltransferase domain of PCAF but not that of CBP/p300 is required for stimulating FKLF2 DNA binding activity. These results demonstrate that CBP/p300 and PCAF stimulate FKLF2 transcriptional activity at least by enhancing its DNA binding. The acetyltransferase activities of CBP/p300 and PCAF play a distinct role in stimulating FKLF2 transcription and DNA binding.