Repetitive DNA promotes RNAi-mediated heterochromatin formation via an anti-silencing factor in fission yeast

Introductory paragraph

In most eukaryotes, constitutive heterochromatin defined by H3K9me2/me3 is enriched on repetitive DNA, such as the satellite repeats of pericentromeres¹. Furthermore, repetitive transgenes often cause the formation of silent heterochromatin in diverse model organisms². Although these facts suggest that the repetition itself promotes heterochromatin formation, the mechanism by which this occurs is still unclear^3–7. Here, using Schizosaccharomyces pombe, we show that tandemly repeated reporter genes promote RNA interference (RNAi)-mediated heterochromatin formation in cooperation with an anti-silencing factor. The repeated gene itself does not cause heterochromatin formation; however, once the RNAi recognizes it via artificial small RNAs, the repeated gene starts producing cognate small RNAs to autonomously maintain heterochromatin. This depends on the number of repeats and an anti-silencing factor Epe1, which removes H3K9me and derepresses transcription of genes underlying heterochromatin. Our results suggest that an anti-silencing factor generates sufficient transcripts for the activation of RNAi when repetitive DNA underlies silent heterochromatin.