Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing

被引:130
作者
Emre, NCT
Ingvarsdottir, K
Wyce, A
Wood, A
Krogan, NJ
Henry, KW
Li, KQ
Marmorstein, R
Greenblatt, JF
Shilatifard, A
Berger, SL [1 ]
机构
[1] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19024 USA
[2] Univ Toronto, Dept Med Genet, Toronto, ON M5G 1L6, Canada
[3] St Louis Univ, Ctr Canc, Dept Biochem & Mol Biol, St Louis, MO 63110 USA
基金
美国国家科学基金会; 美国国家卫生研究院; 加拿大健康研究院;
关键词
D O I
10.1016/j.molcel.2005.01.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Low levels of histone covalent modifications are associated with gene silencing at telomeres and other regions in the yeast S. cerevisiae. Although the histone deacetylase Sir2 maintains low acetylation, mechanisms responsible for low H2B ubiquitylation and low H3 methylation are unknown. Here, we show that the ubiquitin protease Ubp10 targets H2B for deubiquitylation, helping to localize Sir2 to the telomere. Ubp10 exhibits reciprocal Sir2-dependent preferential localization proximal to telomeres, where Ubp10 serves to maintain low H2B Lys123 ubiquitylation in this region and, through previously characterized crosstalk, maintains low H3 Lys4 and Lys79 methylation in a slightly broader region. Ubp10 is also localized to the rDNA locus, a second silenced domain, where it similarly maintains low histone methylation. We compare Ubp10 to Ubp8, the SAGA-associated H2B deubiquitylase involved in gene activation, and show that telomeric and gene-silencing functions are specific to Ubp10. Our results suggest that these H2B-deubiquitylating enzymes have distinct genomic functions.
引用
收藏
页码:585 / 594
页数:10
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