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.

Akiko Okita et al. demonstrate that heterochromatin suppresses gross chromosomal rearrangements by repressing Tfs1/TFIIS-dependent transcription of repetitive sequences. This study underscores the role of heterochromatin for maintaining chromosome stability.

Details

Title
Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription
Author
Okita, Akiko K 1 ; Faria, Zafar 1 ; Su, Jie 1 ; Dayalini, Weerasekara 1 ; Kajitani Takuya 2 ; Takahashi, Tatsuro S 3   VIAFID ORCID Logo  ; Kimura, Hiroshi 4   VIAFID ORCID Logo  ; Murakami Yota 5 ; Masukata Hisao 1 ; Nakagawa Takuro 1   VIAFID ORCID Logo 

1  Osaka University, Department of Biological Sciences, Graduate School of Science, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
2  Hokkaido University, Department of Chemistry, Faculty of Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691); Cornell University, Department of Molecular Biology and Genetics, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
3  Osaka University, Department of Biological Sciences, Graduate School of Science, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); Kyushu University, Department of Biology, Faculty of Science, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
4  Tokyo Institute of Technology, Cell Biology Center, Institute of Innovative Research, Yokohama, Japan (GRID:grid.32197.3e) (ISNI:0000 0001 2179 2105) 
5  Hokkaido University, Department of Chemistry, Faculty of Science, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-018-0251-z
ProQuest document ID
2389680568
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.