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

Nearly half the human genome is comprised of repetitive DNA, including short interspersed nuclear elements (SINEs) such as Alu. SINEs 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 through chromosomal rearrangements between nonallelic SINEs at distinct loci. SINE DNA is heavily methylated and this is thought to suppress its accessibility and transcription, thereby protecting against retrotransposition. However, we provide several lines of evidence that methylated SINE DNA is occupied genome-wide by RNA polymerase III, including the use of high-throughput bisulphite sequencing of ChIP DNA (ChIP-BS-Seq). Loss of DNA methylation has little effect on expression of SINEs or their accessibility to transcription machinery. We present evidence that methylation of histones rather than DNA plays a dominant role in suppressing SINE expression. RPC155 ChIP DNA was bisulfite-converted prior to sequencing (ChIP-Bis-seq). A single library was prepared for the ChIP-Bis-seq and two libraries were prepared for Input DNA from the same sonicate.