CAGE-seq to identify effects of Epe1 OP on transcription start sites in fission yeast.

In eukaryotic cells, histone H3 lysine 9 methylation (H3K9me) defines silent chromatin, which represses gene expression and assembles constitutive heterochromatin. The epigenetic eraser H3K9 demethylase removes H3K9me, which enables the dynamic regulation of epigenetic states, such as facultative heterochromatin. However, how the cell manages the epigenetic erasing at constitutive heterochromatin is not fully understood. Using fission yeast, here we show that H3K9 demethylation factor Epe1, which removes ectopic H3K9me at euchromatin, paradoxically activates H3K9 methylation at constitutive heterochromatin via RNA interference (RNAi). Genome-wide analysis CAGE-seq reveals that Epe1 overproduction results in activation of widespread transcription stat site within heterochromatin.