Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene
- 2 August 2004
- journal article
- Published by Springer Nature in Oncogene
- Vol. 23 (44) , 7391-7398
- https://doi.org/10.1038/sj.onc.1207972
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 p21waf1 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 p21waf1. 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 p21waf1 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.Keywords
This publication has 22 references indexed in Scilit:
- Phosphorylation of Serine 2 within the RNA Polymerase II C-Terminal Domain Couples Transcription and 3′ End ProcessingMolecular Cell, 2004
- The CTD codeNature Structural & Molecular Biology, 2003
- Strange bedfellows: polyadenylation factors at the promoterGenes & Development, 2003
- Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongationGenes & Development, 2003
- Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-α-inducible genesNature Cell Biology, 2002
- An extensive network of coupling among gene expression machinesNature, 2002
- Functional Interaction of STAT3 Transcription Factor with the Coactivator NcoA/SRC1aJournal of Biological Chemistry, 2002
- Histone Acetyltransferase Complexes Stabilize SWI/SNF Binding to Promoter NucleosomesCell, 2001
- The language of covalent histone modificationsNature, 2000
- Stat3 as an OncogenePublished by Elsevier ,1999