Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2.
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.
Song
Chao-Zhong
CZ
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Keller
Kimberly
K
Murata
Ken
K
Asano
Haruhiko
H
Stamatoyannopoulos
George
G
D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005914:Globins / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D020014:K562 Cells; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004247:DNA; D005914:Globins; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C486423:KLF13 protein, human