Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing.
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.
Emre
N C Tolga
NC
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19024, USA.
Ingvarsdottir
Kristin
K
Wyce
Anastasia
A
Wood
Adam
A
Krogan
Nevan J
NJ
Henry
Karl W
KW
Li
Keqin
K
Marmorstein
Ronen
R
Greenblatt
Jack F
JF
Shilatifard
Ali
A
Berger
Shelley L
SL
D000107:Acetylation; D047369:Chromatin Immunoprecipitation; D004275:DNA, Ribosomal; D015536:Down-Regulation; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009687:Nuclear Proteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000502:physiology*; D016615:Telomere / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
D004275:DNA, Ribosomal; D006657:Histones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D025801:Ubiquitin; C403282:UBP10 protein, S cerevisiae; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine