p27Kip1, PCAF and PAX5 cooperate in the transcriptional regulation of specific target genes
| Autor: | Jonatan Martinez, Albert Jordan, Rosa Aligué, Anna Perearnau, Serena Orlando, Maria Jesús Pujol, Edurne Gallastegui, Anna Bigas, Abul B. M. M. K. Islam, Oriol Bachs |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación 'la Caixa', Universitat de Barcelona |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transcription Genetic Cèl·lules PAX5 Transcription Factor Repressor P300-CBP Transcription Factors Biology Cromatina 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Regulació genètica Genetics Transcriptional regulation Animals Humans p300-CBP Transcription Factors Transcription factor Cells Cultured Regulation of gene expression Binding Sites Genetic regulation Gene regulation Chromatin and Epigenetics Proteins HCT116 Cells Epigenètica Chromatin Cell biology 030104 developmental biology PCAF Gene Expression Regulation Tissue Array Analysis 030220 oncology & carcinogenesis MCF-7 Cells Epigenetics Cyclin-Dependent Kinase Inhibitor p27 Protein Binding |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Recercat. Dipósit de la Recerca de Catalunya Nucleic Acids Research Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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. Ministerio de Economía y Competitividad (MINECO) [SAF2012-38078 to O.B. and BFU2015-65311-R to R.A.]; Instituto de Salud Carlos III [RD12/0036/0054 to O.B. and CB16/12/00244 (CIBERONC) to A.B.]; ‘La Caixa’ Foundation 2016-052407 (to R.A.). Funding for open access charge: MInisterio the Economia y Competitividad, Spain La Caixa Foundation. Spain. |
| Databáze: | OpenAIRE |
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