Transcription-induced chromatin association of RNA surveillance factors mediates facultative heterochromatin formation in fission yeast.

Facultative heterochromatin is reversibly established and disrupted during differentiation, but its regulation remains mechanistically unclear. Here, we show that two meiotic gene loci in fission yeast, mei4 and ssm4, comprise facultative heterochromatin that is regulated in a developmental stage-dependent manner. This heterochromatin coordinates expression levels by associating with a chromodomain protein Chp1 and an antisilencing factor Epe1. It has been recently shown that an RNA surveillance machinery for eliminating meiotic gene transcripts, which involves a cis-element called the determinant of selective removal (DSR) and transacting factors, Mmi1 and Red1, also participates in heterochromatin formation at the meiotic genes, but the molecular mechanism underlying the process is largely unknown. By dissecting the mei4 gene, we identified a region that promotes DSR-dependent methylation of histone H3 lysine 9 (H3K9). Integration of this mei4 region together with DSR into an unrelated gene results in ectopic H3K9 methylation. Moreover, our results suggest that transcription of these elements induces chromatin association of Mmi1, which, in turn, recruits Red1 interacting with Clr4/Suv39h H3K9 methyltransferase. Mmi1 remains associated in cells lacking Red1, suggesting that the recruitment of Red1 follows the chromatin association of Mmi1. Overall, we provide detailed insights into the facultative heterochromatin regulation in fission yeast.