p27Kip1, PCAF and PAX5 cooperate in the transcriptional regulation of specific target genes.
The cyclin-dependent kinase inhibitor p27Kip1 (p27) also behaves as a transcriptional repressor. Data showing that the p300/CBP-associated factor (PCAF) acetylates p27 inducing its degradation suggested that PCAF and p27 could collaborate in the regulation of transcription. However, this possibility remained to be explored. We analyzed here the transcriptional programs regulated by PCAF and p27 in the colon cancer cell line HCT116 by chromatin immunoprecipitation sequencing (ChIP-seq). We identified 269 protein-encoding genes that contain both p27 and PCAF binding sites being the majority of these sites different for PCAF and p27. PCAF or p27 knock down revealed that both regulate the expression of these genes, PCAF as an activator and p27 as a repressor. The double knock down of PCAF and p27 strongly reduced their expression indicating that the activating role of PCAF overrides the repressive effect of p27. We also observed that the transcription factor Pax5 interacts with both p27 and PCAF and that the knock down of Pax5 induces the expression of p27/PCAF target genes indicating that it also participates in the transcriptional regulation mediated by p27/PCAF. In summary, we report here a previously unknown mechanism of transcriptional regulation mediated by p27, Pax5 and PCAF.
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Anna
A
Perearnau
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Serena
S
Orlando
Department of Genetic Engineering and Biotechnology University of Dhaka, Dhaka 1000, Bangladesh.
Abul B M M K
ABMMK
Islam
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Edurne
E
Gallastegui
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Jonatan
J
Martínez
Department of Molecular Genomics, Molecular Biology Institute of Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), 08029 Barcelona, Spain.
Albert
A
Jordan
Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), CIBERONC, 08003 Barcelona, Spain.
Anna
A
Bigas
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Rosa
R
Aligué
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Maria Jesús
MJ
Pujol
Department of Biomedical Sciences, University of Barcelona-IDIBAPS, CIBERONC, 08036 Barcelona, Spain.
Oriol
O
Bachs
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D051757:PAX5 Transcription Factor / Q000502:physiology*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics; D046888:Tissue Array Analysis; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000502:physiology*; D000099224:p300-CBP-Associated Factor
D002843:Chromatin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051757:PAX5 Transcription Factor; D011506:Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C436291:CDKN1B protein, human; C497281:PAX5 protein, human