p21 as a transcriptional co-repressor of S-phase and mitotic control genes.

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Serval ID
serval:BIB_9EB2189F7145
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
p21 as a transcriptional co-repressor of S-phase and mitotic control genes.
Journal
PLoS One
Author(s)
Ferrándiz N., Caraballo J.M., García-Gutierrez L., Devgan V., Rodriguez-Paredes M., Lafita M.C., Bretones G., Quintanilla A., Muñoz-Alonso M.J., Blanco R., Reyes J.C., Agell N., Delgado M.D., Dotto G.P., León J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Volume
7
Number
5
Pages
e37759
Language
english
Abstract
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.
Keywords
Cell Line, Cluster Analysis, Co-Repressor Proteins/metabolism, Computational Biology/methods, Cyclin-Dependent Kinase 2/metabolism, Cyclin-Dependent Kinase Inhibitor p21/chemistry, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Cyclins/genetics, Gene Expression Profiling, Gene Expression Regulation, Humans, K562 Cells, Keratinocytes/metabolism, Mitosis/genetics, Promoter Regions, Genetic, Protein Binding, S Phase/genetics, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
23/07/2012 9:51
Last modification date
20/08/2019 15:04
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