Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene (original) (raw)

• Original Paper
• Published: 02 August 2004

Oncogene volume 23, pages 7391–7398 (2004)Cite this article

Abstract

STAT transcription factors (signal transducers and activators of transcription) are cytoplasmic proteins that induce gene activation in response to cytokine receptor stimulation. Following tyrosine phosphorylation, STAT proteins translocate into the nucleus and activate specific target genes. We have previously reported that STAT3 activates the expression of the p21_waf1_ gene through its association with the NcoA/SRC1a and CBP coactivators. In this study, we explore the role of BRG1, a component of the SWI/SNF chromatin-remodeling complex, and the role of cdk9, a component of the elongation factor P-TEFb, in the STAT3-mediated expression of p21_waf1_. We found using pull-down experiments and co-immunoprecipitation assays that both proteins associate with STAT3. Chromatin immunoprecipitation (ChIP) experiments indicate that STAT3 DNA binding results in histone H3 acetylation and BRG1 recruitment. Using Southern blot analysis, we found that the loading of BRG1 is followed by an increased accessibility of the proximal p21_waf1_ promoter and by the association of RNA polymerase II. As a next step, STAT3 then recruits the cdk9 kinase to phosphorylate the carboxy-terminal domain of the RNA polymerase at serine 2. Accordingly, the elongating form of the polymerase can be detected by ChIP experiments on the coding region of the gene, probably initiating mRNA synthesis. Therefore, STAT3 not only promotes the initiation of transcription but also regulates chromatin remodeling and transcription elongation through its interaction with BRG1 and cdk9.

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Acknowledgements

We thank Hans Clevers for the gift of expressing vectors and cell lines. This work was supported by a fellowship (to SG) from the Ministere de la Recherche et de la Technologie and by a grant from the Ligue Pour la Recherche Sur le Cancer, Comite Departemental de Maine et Loire.

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Authors and Affiliations

1. INSERM U564, 4 rue Larrey, CHU Angers, Angers Cedex, 49033, France
   Sandrine Giraud, Sylvie Avril & Olivier Coqueret
2. Department of Immunology and Centre for Biomedical Genetics, University Medical Centre Utrecht, The Netherlands
   Adam Hurlstone

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1. Sandrine Giraud
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2. Adam Hurlstone
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3. Sylvie Avril
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4. Olivier Coqueret
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Correspondence toOlivier Coqueret.

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Giraud, S., Hurlstone, A., Avril, S. et al. Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21_waf1_ gene.Oncogene 23, 7391–7398 (2004). https://doi.org/10.1038/sj.onc.1207972

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• Received: 20 April 2004
• Revised: 04 June 2004
• Accepted: 09 June 2004
• Published: 02 August 2004
• Issue Date: 23 September 2004
• DOI: https://doi.org/10.1038/sj.onc.1207972

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