title: Bromodomain protein 7 interacts with PRMT5 and PRC2, and is involved in transcriptional repression of their target genes.
abstract: Histone modification regulates gene expression, and one major regulatory step in this process is the ability of proteins that recognize epigenetic marks to recruit enzymes required to specify transcriptional outcome. Here we show that BRD7 is a component of hSWI-SNF complexes that interacts with PRMT5 and PRC2. Recruitment studies revealed that BRD7 co-localizes with PRMT5 and PRC2 on 'suppressor of tumorigenecity 7' (ST7) and retinoblastoma-like protein 2 (RBL2) promoters in patient-derived B cell lines, and that its association with these target genes correlates with hypermethylation of H3R8, H4R3 and H3K27. Furthermore, inhibition of BRD7 expression reduces PRMT5 and PRC2 recruitment to ST7 and RBL2 promoters; however, only ST7 becomes transcriptionally derepressed. Evaluation of the PRMT5- and PRC2-induced epigenetic marks revealed that while H3(Me(2))R8, H4(Me(2))R3 and H3(Me(3))K27 marks are erased from the ST7 promoter, demethylation of RBL2 promoter histones is incomplete. We also show that the arginine demethylase (RDM) JMJD6, which can erase PRMT5-induced H4R3 methylation, and the H3K27-lysine-specific demethylases, KDM6A/UTX and KDM6B/JMJD3, are differentially recruited to ST7 and RBL2. These findings highlight the role played by BRD7 in PRMT5- and PRC2-induced transcriptional silencing, and indicate that recruitment of specific RDMs and KDMs is required for efficient transcriptional derepression.
authors: Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, Ohio, OH 43210, USA.
authors: Sookil
authors: S
authors: Tae
authors: Vrajesh
authors: V
authors: Karkhanis
authors: Kevin
authors: K
authors: Velasco
authors: Mariana
authors: M
authors: Yaneva
authors: Hediye
authors: H
authors: Erdjument-Bromage
authors: Paul
authors: P
authors: Tempst
authors: Saïd
authors: S
authors: Sif
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D056466:Histone Demethylases / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D012097:Repressor Proteins / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D056466:Histone Demethylases; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; D012097:Repressor Proteins; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C493837:RBL2 protein, human; C412123:ST7 protein, human; C430461:SUZ12 protein, human; C400529:PRMT5 protein, human; C478359:WDR77 protein, human