期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 586, 期 -, 页码 150-156出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.11.077
关键词
Histone; H2A; Z; CENP-A; CENP-C; Chromosome segregation; Transcription
资金
- Tohoku Medical and Pharmaceutical University
The absence of TBS-III leads to reduced chromatin binding and total amount of centromere proteins, as well as up-regulated transcription at the centromere during M-phase. Ectopic transcription through the centromere displaces key centromere proteins, destabilizing the interaction between centromeres and microtubules, and causing defective chromosome segregation. The identification of new roles for histone binding residues in TBS-III provides new insights into nucleosome function during chromosome segregation.
Bi-oriented attachment of microtubules to the centromere is a pre-requisite for faithful chromosome segregation during mitosis. Budding yeast have point centromeres containing the cis-element proteins CDE-I,-II, and-III, which interact with trans-acting factors such as Cbf1, Cse4, and Ndc10. Our previous genetic screens, using a comprehensive library of histone point mutants, revealed that the TBS-I,-II, and-III regions of nucleosomes are required for faithful chromosome segregation. In TBS-III deficient cells, peri-centromeric nucleosomes containing the H2A.Z homolog Htz1 are lacking, however, it is unclear why chromosome segregation is defective in these cells. Here, we show that, in cells lacking TBS-III, both chromatin binding at the centromere and the total amount of some of the centromere proteins are reduced, and transcription through the centromere is up-regulated during M-phase. Moreover, the chromatin binding of Cse4, Mif2, Cbf1, Ndc10, and Scm3 was reduced upon ectopic transcription through the centromere in wild-type cells. These results suggest that transcription through the centromere displaces key centromere proteins and, consequently, destabilizes the interaction between centromeres and microtubules, leading to defective chromosome segregation. The identification of new roles for histone binding residues in TBS-III will shed new light on nucleosome function during chromosome segregation. (c) 2021 Elsevier Inc. All rights reserved.
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