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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Pal
authors.forename: Romy
authors.initials: R
authors.lastname: Yun
authors.forename: Antara
authors.initials: A
authors.lastname: Datta
authors.forename: Lynne
authors.initials: L
authors.lastname: Lacomis
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Jitendra
authors.initials: J
authors.lastname: Kumar
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Saïd
authors.initials: S
authors.lastname: Sif
mesh_terms: D001221:Aspartate Carbamoyltransferase / Q000235:genetics* / Q000378:metabolism; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases; D047630:Depsipeptides; D004791:Enzyme Inhibitors / Q000378:metabolism; D006367:HeLa Cells; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D006657:Histones; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C019820:carbamoyl phosphate synthase-aspartatecarbamoyl transferase complex; C087123:romidepsin; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D001221:Aspartate Carbamoyltransferase; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)