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

Varshney, D., Vavrova-Anderson, J. , Oler, A. J., Cowling, V. H., Cairns, B. R. and White, R. J. (2015) SINE transcription by RNA polymerase III is suppressed by histone methylation but not DNA methylation. Nature Communications, 6, 6569. (doi:10.1038/ncomms7569) (PMID:25798578) (PMCID:PMC4382998)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Anderson, Dr Jana and White, Prof Robert and Varshney, Mr Dhaval
Authors: Varshney, D., Vavrova-Anderson, J., Oler, A. J., Cowling, V. H., Cairns, B. R., and White, R. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 Macmillan Publishers Limited
First Published:First published in Nature Communications 6:6569
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
367861Molecular functions in diseaseRobert WhiteWellcome Trust (WELLCOME)073424/Z/03/ZRI CANCER SCIENCES