title: SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation.
abstract: Short interspersed nuclear elements (SINEs), such as Alu, spread by retrotransposition, which requires their transcripts to be copied into DNA and then inserted into new chromosomal sites. This can lead to genetic damage through insertional mutagenesis and chromosomal rearrangements between non-allelic SINEs at distinct loci. SINE DNA is heavily methylated and this was thought to suppress its accessibility and transcription, thereby protecting against retrotransposition. Here we provide several lines of evidence that methylated SINE DNA is occupied by RNA polymerase III, including the use of high-throughput bisulphite sequencing of ChIP DNA. We find that loss of DNA methylation has little effect on accessibility of SINEs to transcription machinery or their expression in vivo. In contrast, a histone methyltransferase inhibitor selectively promotes SINE expression and occupancy by RNA polymerase III. The data suggest that methylation of histones rather than DNA plays a dominant role in suppressing SINE transcription.
authors: 1] College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK [2] The MRC Protein Phosphorylation Unit, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors: Dhaval
authors: D
authors: Varshney
authors: College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Jana
authors: J
authors: Vavrova-Anderson
authors: 1] Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA [2] Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
authors: Andrew J
authors: AJ
authors: Oler
authors: The MRC Protein Phosphorylation Unit, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors: Victoria H
authors: VH
authors: Cowling
authors: 1] Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA [2] Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
authors: Bradley R
authors: BR
authors: Cairns
authors: 1] College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK [2] Department of Biology, University of York, York YO10 5DD, UK.
authors: Robert J
authors: RJ
authors: White
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D042421:Histone Code / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D008745:Methylation; D051379:Mice; D012320:RNA Polymerase III / Q000378:metabolism*; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C066141:MBD1 protein, human; C489325:MBD2 protein, human; C489323:Mbd1 protein, mouse; C489326:Mbd2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D014157:Transcription Factors; D012320:RNA Polymerase III