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

Akiko K. Okita, Faria Zafar, Jie Su, Dayalini Weerasekara, Takuya Kajitani, Tatsuro Takahashi, Hiroshi Kimura, Yota Murakami, Hisao Masukata, Takuro Nakagawa

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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.

Original languageEnglish
Article number17
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Methylation
Heterochromatin
RNA Polymerase II
Centromere
centromeres
heterochromatin
Transcription
transcription (genetics)
Nucleic Acid Repetitive Sequences
Methyltransferases
Chromosomes
Histones
Yeast
Lysine
DNA-directed RNA polymerase
Transcription Factors
mutation
methylation
Mutation
Isochromosomes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription. / Okita, Akiko K.; Zafar, Faria; Su, Jie; Weerasekara, Dayalini; Kajitani, Takuya; Takahashi, Tatsuro; Kimura, Hiroshi; Murakami, Yota; Masukata, Hisao; Nakagawa, Takuro.

In: Communications Biology, Vol. 2, No. 1, 17, 01.12.2019.

Research output: Contribution to journalArticle

Okita, AK, Zafar, F, Su, J, Weerasekara, D, Kajitani, T, Takahashi, T, Kimura, H, Murakami, Y, Masukata, H & Nakagawa, T 2019, 'Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription', Communications Biology, vol. 2, no. 1, 17. https://doi.org/10.1038/s42003-018-0251-z
Okita, Akiko K. ; Zafar, Faria ; Su, Jie ; Weerasekara, Dayalini ; Kajitani, Takuya ; Takahashi, Tatsuro ; Kimura, Hiroshi ; Murakami, Yota ; Masukata, Hisao ; Nakagawa, Takuro. / Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription. In: Communications Biology. 2019 ; Vol. 2, No. 1.
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