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

Nature Communications
Dhaval VarshneyRobert J White

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.

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Citations

Mar 5, 2016·Mobile Genetic Elements·Dhaval VarshneyRobert J White
Apr 14, 2016·Trends in Biochemical Sciences·Aneeshkumar G Arimbasseri, Richard J Maraia
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Apr 2, 2021·Annual Review of Genomics and Human Genetics·Xiao-Ou ZhangZhiping Weng

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Datasets Mentioned

BETA
J02459.1
GSE38794

Methods Mentioned

BETA
transfections
immunoprecipitation
PCR
ChIP
restriction
phosphotransferase
in vitro transcription
PCRs
ChIP-Seq
ChIP-BS-Seq

Software Mentioned

novoalign
PeakShiftFinder
USeq
novoindex
ScanSeqs
NovoalignParser
ScoreMethylatedRegions
novoalign PE PCR Primer
BisSeq
DefinedRegionScanSeqs

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