Wajapeyee, NarendraMalonia, Sunil K.Palakurthy, Rajendra KumarGreen, Michael R.2022-08-232022-08-232013-10-152015-10-08Genes Dev. 2013 Oct 15;27(20):2221-6. doi: 10.1101/gad.227413.113. Epub 2013 Oct 8. <a href="http://dx.doi.org/10.1101/gad.227413.113">Link to article on publisher's site</a>0890-9369 (Linking)10.1101/gad.227413.11324105743https://hdl.handle.net/20.500.14038/30507We previously identified 28 cofactors through which a RAS oncoprotein directs transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we performed RNAi-based epistasis experiments and found that RAS-directed silencing occurs through a highly ordered pathway that is initiated by binding of ZFP354B, a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal that silencing requires continuous function of RAS and its cofactors and can be rapidly reversed, which may have therapeutic implications for reactivation of silenced TSGs in RAS-positive cancers.en-US© 2013 Wajapeyee et al.; Published by Cold Spring Harbor Laboratory Press.This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see <a href="http://genesdev.cshlp.org/site/misc/terms.xhtml">http://genesdev.cshlp.org/site/misc/terms.xhtml</a>). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at <a href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</a>.http://creativecommons.org/licenses/by-nc/3.0/AnimalsAntigens, CD95DNA MethylationEpigenesis, Genetic*Gene Expression Regulation, Neoplastic*Gene Silencing*Genes, Tumor SuppressorMiceModels, BiologicalNIH 3T3 CellsProtein BindingRNA InterferenceSignal Transductionras ProteinsDNMT1RASRNA interferenceZFP354Bepigenetic silencingepistasis analysisCancer BiologyCell and Developmental BiologyGenetics and GenomicsOncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressorsJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1786&context=faculty_pubs&unstamped=1https://escholarship.umassmed.edu/faculty_pubs/7857693436faculty_pubs/785