mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad Journal Article
| Authors: | Pal, S.; Yun, R.; Datta, A.; Lacomis, L.; Erdjument-Bromage, H.; Kumar, J.; Tempst, P.; Sif, S. |
| Article Title: | mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad |
| Abstract: | The role of hSWI/SNF complexes in transcriptional activation is well characterized; however, little is known about their function in transcriptional repression. We have previously shown that subunits of the mSin3A/histone deacetylase 2 (HDAC2) corepressor complex copurify with hSWI/SNF complexes. Here we show that the type II arginine-specific methyltransferase PRMT5, which is involved in cyclin E repression, can be found in association with Brg1 and hBrm-based hSWI/SNF complexes. We also show that hSWI/SNF-associated PRMT5 can methylate hypoacetylated histones H3 and H4 more efficiently than hyperacetylated histones H3 and H4. Protein-protein interaction studies indicate that PRMT5 and mSin3A interact with the same hSWI/SNF subunits as those targeted by c-Myc. These observations prompted us to examine the expression profile of the c-Myc target genes, carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) and nucleolin (nuc). We found that cad repression is altered in cells that express inactive Brg1 and in cells treated with the HDAC inhibitor depsipeptide. Using chromatin immunoprecipitation assays, we found that Brg1, mSin3A, HDAC2, and PRMT5 are directly recruited to the cad promoter. These results suggest that hSWI/SNF complexes, through their ability to interact with activator and repressor proteins, control expression of genes involved in cell growth and proliferation. |
| Keywords: | controlled study; unclassified drug; human cell; methylation; promoter region; cell proliferation; chromosomal proteins, non-histone; cell growth; protein protein interaction; transcription initiation; protein; transcription, genetic; hela cells; transcription factors; nuclear proteins; gene expression regulation; methyltransferase; transcription regulation; enzyme inhibitors; histone h3; gene repression; recombinant proteins; immunoprecipitation; multienzyme complexes; proto-oncogene proteins c-myc; enzyme subunit; repressor proteins; histones; histone deacetylases; depsipeptides; dna helicases; oncogene myc; peptides, cyclic; cyclin e; histone deacetylase; depsipeptide; histone deacetylase 2; histone h4; protein methyltransferases; promoter regions (genetics); nucleolin; protein prmt5; humans; human; priority journal; article; aspartate carbamoyltransferase; carbamate kinase; dihydroorotase; protein brg1; carbamoyl-phosphate synthase (glutamine-hydrolyzing) |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 23 |
| Issue: | 21 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2003-11-01 |
| Start Page: | 7475 |
| End Page: | 7487 |
| Language: | English |
| DOI: | 10.1128/mcb.23.21.7475-7487.2003 |
| PUBMED: | 14559996 |
| PROVIDER: | scopus |
| PMCID: | PMC207647 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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