Genome-wide impact of the BRG1 SWI/SNF chromatin remodeler on the transforming growth factor β transcriptional program Journal Article
| Authors: | Xi, Q.; He, W.; Zhang, X. H. F.; Le, H. V.; Massague, J. |
| Article Title: | Genome-wide impact of the BRG1 SWI/SNF chromatin remodeler on the transforming growth factor β transcriptional program |
| Abstract: | The transcription factors Smad2 and Smad3 mediate a large set of gene responses induced by the cytokine transforming growth factor β (TGFβ), but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170, and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFβ stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems, we defined the BRG1 dependence of the TGFβ transcriptional program genome-wide. Most TGFβ gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFβ-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFβ action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; human cell; gene deletion; protein function; sensitivity analysis; mass spectrometry; reverse transcription polymerase chain reaction; genes; smad2 protein; smad3 protein; transforming growth factor beta; cell line; rna, small interfering; protein interaction; transcription, genetic; in vitro study; transfection; transcription factors; nuclear proteins; gene expression regulation; oligonucleotide array sequence analysis; chromatin; recombinant proteins; transforming growth factors; epithelium cell; keratinocytes; dna helicases; genome, human; cells; open reading frames; protein swi; transcription factor snf; promoter regions (genetics); growth kinetics; human epithelial cells; transcriptional programs; brg1 protein |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 283 |
| Issue: | 2 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2008-01-11 |
| Start Page: | 1146 |
| End Page: | 1155 |
| Language: | English |
| DOI: | 10.1074/jbc.M707479200 |
| PUBMED: | 18003620 |
| PROVIDER: | scopus |
| PMCID: | PMC2692279 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 22" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Source: Scopus" |
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