RRC ID 64255
Author Okita AK, Zafar F, Su J, Weerasekara D, Kajitani T, Takahashi TS, Kimura H, Murakami Y, Masukata H, Nakagawa T.
Title Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription.
Journal Commun Biol
Abstract Heterochromatin, characterized by histone H3 lysine 9 (H3K9) methylation, assembles on repetitive regions including centromeres. Although centromeric heterochromatin is important for correct segregation of chromosomes, its exact 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 were located in centromere repeats. H3K9A and H3K9R mutations also increased GCRs, suggesting that Clr4 suppresses centromeric GCRs via H3K9 methylation. HP1 homologs Swi6 and Chp2 and the RNAi component Chp1 were the chromodomain proteins essential for full suppression of GCRs. Remarkably, mutations in RNA polymerase II (RNAPII) or Tfs1/TFIIS, the transcription factor that facilitates restart of RNAPII after backtracking, specifically bypassed the requirement of Clr4 for suppressing GCRs. These results demonstrate that heterochromatin suppresses GCRs by repressing Tfs1-dependent transcription of centromere repeats.
Volume 2
Pages 17
Published 2019-1-1
DOI 10.1038/s42003-018-0251-z
PII 251
PMID 30652128
PMC PMC6329695
MeSH Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Centromere / metabolism* Chromosomal Proteins, Non-Histone / metabolism Heterochromatin / metabolism* Histone-Lysine N-Methyltransferase / genetics Histones / genetics Isochromosomes / genetics* Methylation Plasmids / genetics RNA Interference RNA Polymerase II / genetics Repressor Proteins / metabolism Schizosaccharomyces / genetics* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Transcription, Genetic / genetics* Transcriptional Elongation Factors / metabolism*
Resource
Yeast