SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation

Dhaval Varshney (), Jana Vavrova-Anderson, Andrew J. Oler, Victoria H. Cowling, Bradley R. Cairns and Robert J. White ()
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Dhaval Varshney: College of Medical, Veterinary and Life Sciences, University of Glasgow
Jana Vavrova-Anderson: College of Medical, Veterinary and Life Sciences, University of Glasgow
Andrew J. Oler: Huntsman Cancer Institute, University of Utah School of Medicine
Victoria H. Cowling: The MRC Protein Phosphorylation Unit, University of Dundee
Bradley R. Cairns: Huntsman Cancer Institute, University of Utah School of Medicine
Robert J. White: College of Medical, Veterinary and Life Sciences, University of Glasgow

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7569

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