Bromodomain protein 7 interacts with PRMT5 and PRC2, and is involved in transcriptional repression of their target genes Journal Article

   

Authors:	Tae, S.; Karkhanis, V.; Velasco, K.; Yaneva, M.; Erdjument-Bromage, H.; Tempst, P.; Sif, S.
Article 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(Me2)R8, H4(Me2)R3 and H3(Me3)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. © 2011 The Author(s).
Keywords:	controlled study; protein expression; unclassified drug; human cell; promoter region; protein localization; mantle cell lymphoma; gene expression; protein protein interaction; hela cell; b lymphocyte; tumor suppressor gene; transcription regulation; chromatin immunoprecipitation; gene repression; membrane protein; binding protein; chronic lymphatic leukemia; repressor protein; protein p130; protein arginine methyltransferase; histone methylation; arginine demethylase; bromodomain protein 7; lysine specific demethylase; mep50 protein; oxygenase; polycomb repressor complex 2; prmt5 protein; protein swi; suppressor of tumorigenicity 7; suz12 protein; transcription factor snf
Journal Title:	Nucleic Acids Research
Volume:	39
Issue:	13
ISSN:	0305-1048
Publisher:	Oxford University Press
Date Published:	2011-07-01
Start Page:	5424
End Page:	5438
Language:	English
DOI:	10.1093/nar/gkr170
PROVIDER:	scopus
PMCID:	PMC3141267
PUBMED:	21447565
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80052252127&partnerID=40&md5=6d834356603664033443dcaf92b6341c
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 3 October 2011" - "CODEN: NARHA" - "Source: Scopus"

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