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p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes
It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360621/ https://www.ncbi.nlm.nih.gov/pubmed/22662213 http://dx.doi.org/10.1371/journal.pone.0037759 |
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author | Ferrándiz, Nuria Caraballo, Juan M. García-Gutierrez, Lucía Devgan, Vikram Rodriguez-Paredes, Manuel Lafita, M. Carmen Bretones, Gabriel Quintanilla, Andrea Muñoz-Alonso, M. Jose Blanco, Rosa Reyes, Jose C. Agell, Neus Delgado, M. Dolores Dotto, G. Paolo León, Javier |
author_facet | Ferrándiz, Nuria Caraballo, Juan M. García-Gutierrez, Lucía Devgan, Vikram Rodriguez-Paredes, Manuel Lafita, M. Carmen Bretones, Gabriel Quintanilla, Andrea Muñoz-Alonso, M. Jose Blanco, Rosa Reyes, Jose C. Agell, Neus Delgado, M. Dolores Dotto, G. Paolo León, Javier |
author_sort | Ferrándiz, Nuria |
collection | PubMed |
description | It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes. |
format | Online Article Text |
id | pubmed-3360621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33606212012-06-01 p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes Ferrándiz, Nuria Caraballo, Juan M. García-Gutierrez, Lucía Devgan, Vikram Rodriguez-Paredes, Manuel Lafita, M. Carmen Bretones, Gabriel Quintanilla, Andrea Muñoz-Alonso, M. Jose Blanco, Rosa Reyes, Jose C. Agell, Neus Delgado, M. Dolores Dotto, G. Paolo León, Javier PLoS One Research Article It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes. Public Library of Science 2012-05-25 /pmc/articles/PMC3360621/ /pubmed/22662213 http://dx.doi.org/10.1371/journal.pone.0037759 Text en Ferrándiz et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ferrándiz, Nuria Caraballo, Juan M. García-Gutierrez, Lucía Devgan, Vikram Rodriguez-Paredes, Manuel Lafita, M. Carmen Bretones, Gabriel Quintanilla, Andrea Muñoz-Alonso, M. Jose Blanco, Rosa Reyes, Jose C. Agell, Neus Delgado, M. Dolores Dotto, G. Paolo León, Javier p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title_full | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title_fullStr | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title_full_unstemmed | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title_short | p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes |
title_sort | p21 as a transcriptional co-repressor of s-phase and mitotic control genes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360621/ https://www.ncbi.nlm.nih.gov/pubmed/22662213 http://dx.doi.org/10.1371/journal.pone.0037759 |
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