title: Selective repression of SINE transcription by RNA polymerase III.
abstract: A million copies of the Alu short interspersed nuclear element (SINE) are scattered throughout the human genome, providing ∼11% of our total DNA. SINEs spread by retrotransposition, using a transcript generated by RNA polymerase (pol) III from an internal promoter. Levels of these pol III-dependent Alu transcripts are far lower than might be expected from the abundance of the template. This was believed to reflect transcriptional suppression through DNA methylation, denying pol III access to most SINEs through chromatin-mediated effects. Contrary to expectations, our recent study found no evidence that methylation of SINE DNA reduces its occupancy or expression by pol III. However, histone H3 associated with SINEs is prominently methylated on lysine 9, a mark that correlates with transcriptional silencing. The SUV39 methyltransferases that deposit this mark can be found at many SINEs. Furthermore, a selective inhibitor of SUV39 stimulates pol III recruitment to these loci, as well as SINE expression. These data suggest that methylation of histone H3 rather than DNA may mediate repression of SINE transcription by pol III, at least under the conditions we studied.
authors.affiliation: Centre for Gene Regulation and Expression; University of Dundee ; Dundee, UK.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Varshney
authors.affiliation: College of Medical; Veterinary and Life Sciences; University of Glasgow ; Glasgow, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Vavrova-Anderson
authors.affiliation: Bioinformatics and Computational Biosciences Branch; Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases; National Institutes of Health ; Bethesda, MD USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Oler
authors.affiliation: Department of Oncological Sciences; Huntsman Cancer Institute; University of Utah School of Medicine; Salt Lake City, UT USA; Howard Hughes Medical Institute; University of Utah School of Medicine; Salt Lake City, UT USA.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Cairns
authors.affiliation: Department of Biology; University of York ; York, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: White
keywords: Alu; H3K9; MeCP2; RNA polymerase III; SINE; SUV39; methylation