Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription

Heterochromatin that is characterized by histone H3 lysine 9 (H3K9) methylation assembles on repetitive regions including centromeres. Although centromeric heterochromatin is important for faithful segregation of chromosomes, its role in maintaining centromere integrity remains elusive. Here, we found in fission yeast that heterochromatin suppresses gross chromosomal rearrangements (GCRs) at centromeres. Mutations in Clr4/Suv39 methyltransferase increased the formation of isochromosomes whose breakpoints are present in centromere repeats. H3K9A and H3K9R mutations also increased GCRs, suggesting that Clr4 appears to suppress GCRs via H3K9 methylation. Both HP1 homologs, Swi6 and Chp2, and an RNAi component Chp1 were the chromodomain proteins that are essential for full suppression of GCRs. Remarkably, mutations in RNA polymerase II (RNAPII) or the transcription factors including Tfs1/TFIIS which facilitates restart of backtracked RNAPII specifically bypassed the requirement of Clr4 to s...