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Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells

The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein–protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated...

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Autores principales: Ouellet, Stéphane, Vigneault, François, Lessard, Maryse, Leclerc, Steeve, Drouin, Régen, Guérin, Sylvain L.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702497/
https://www.ncbi.nlm.nih.gov/pubmed/17130157
http://dx.doi.org/10.1093/nar/gkl861
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author Ouellet, Stéphane
Vigneault, François
Lessard, Maryse
Leclerc, Steeve
Drouin, Régen
Guérin, Sylvain L.
author_facet Ouellet, Stéphane
Vigneault, François
Lessard, Maryse
Leclerc, Steeve
Drouin, Régen
Guérin, Sylvain L.
author_sort Ouellet, Stéphane
collection PubMed
description The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein–protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated at the transcriptional level. By conducting both ligation-mediated PCR (LMPCR) and chromatin immunoprecipitation (ChIP) in vivo, we identified a functional target site for the transcription factor, nuclear factor I (NFI), in the basal promoter from the p21 gene. Transfection of recombinant constructs bearing mutations in the p21 NFI site demonstrated that NFI acts as a repressor of p21 gene expression in various types of cultured cells. Inhibition of NFI in human skin fibroblasts through RNAi considerably increased p21 promoter activity suggesting that NFI is a key repressor of p21 transcription. Over-expression of each of the four NFI isoforms in HCT116 cells established that each of them contribute to various extend to the repression of the p21 gene. Most of all, over-expression of NFI-B in doxorubicin, growth-arrested HCT116 increased the proportion of cells in the S-phase of the cell cycle whereas NFI-A and NFI-X reduced it, thereby establishing a role for NFI in the cell cycle dependent expression of p21.
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spelling pubmed-17024972006-12-26 Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells Ouellet, Stéphane Vigneault, François Lessard, Maryse Leclerc, Steeve Drouin, Régen Guérin, Sylvain L. Nucleic Acids Res Molecular Biology The cyclin-dependent kinase inhibitor 1A (CDKN1A), also known as p21 (WAF1/CIP1) modulates cell cycle, apoptosis, senescence and differentiation via specific protein–protein interactions with the cyclins, cyclin-dependent kinase (Cdk), and many others. Expression of the p21 gene is mainly regulated at the transcriptional level. By conducting both ligation-mediated PCR (LMPCR) and chromatin immunoprecipitation (ChIP) in vivo, we identified a functional target site for the transcription factor, nuclear factor I (NFI), in the basal promoter from the p21 gene. Transfection of recombinant constructs bearing mutations in the p21 NFI site demonstrated that NFI acts as a repressor of p21 gene expression in various types of cultured cells. Inhibition of NFI in human skin fibroblasts through RNAi considerably increased p21 promoter activity suggesting that NFI is a key repressor of p21 transcription. Over-expression of each of the four NFI isoforms in HCT116 cells established that each of them contribute to various extend to the repression of the p21 gene. Most of all, over-expression of NFI-B in doxorubicin, growth-arrested HCT116 increased the proportion of cells in the S-phase of the cell cycle whereas NFI-A and NFI-X reduced it, thereby establishing a role for NFI in the cell cycle dependent expression of p21. Oxford University Press 2006-12 2006-11-27 /pmc/articles/PMC1702497/ /pubmed/17130157 http://dx.doi.org/10.1093/nar/gkl861 Text en © 2006 The Author(s).
spellingShingle Molecular Biology
Ouellet, Stéphane
Vigneault, François
Lessard, Maryse
Leclerc, Steeve
Drouin, Régen
Guérin, Sylvain L.
Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title_full Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title_fullStr Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title_full_unstemmed Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title_short Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells
title_sort transcriptional regulation of the cyclin-dependent kinase inhibitor 1a (p21) gene by nfi in proliferating human cells
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702497/
https://www.ncbi.nlm.nih.gov/pubmed/17130157
http://dx.doi.org/10.1093/nar/gkl861
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