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

N. C Tolga Emre; Kristin Ingvarsdottir; Anastasia Wyce; Adam Wood; Nevan J. Krogan; Karl W. Henry; Keqin Li; Ronen Marmorstein; Jack F. Greenblatt; Ali Shilatifard; Shelley L. Berger

doi:10.1016/j.molcel.2005.01.007

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

N. C Tolga Emre, Kristin Ingvarsdottir, Anastasia Wyce, Adam Wood, Nevan J. Krogan, Karl W. Henry, Keqin Li, Ronen Marmorstein, Jack F. Greenblatt, Ali Shilatifard, Shelley L. Berger^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

140 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	585-594
Number of pages	10
Journal	Molecular cell
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2005.01.007
State	Published - Feb 18 2005

Funding

We thank M. Osley for HA-Ub expression plasmid, T. Edlind and K. Struhl for yeast strains, and Jean Dorsey for technical assistance. We acknowledge T. Krishnamoorthy, S. McMahon, and G. Moore for critically reading the manuscript. We thank the Berger lab and especially D. Gottschling for valuable discussions. Research was supported by research grants from the National Institutes of Health (NIH) and National Science Foundation to S.L.B; a National Research Service Award to K.W.H. and NIH training grant awards to K.W.H. and to A.W.; a doctoral fellowship from the University of Pennsylvania BGS to K.L.; the American Cancer Society, NIH, and a Mallinckrodt Foundation Award to A.S.; a doctoral fellowship from the Canadian Institutes of Health Research (CIHR) to N.J.K; the CIHR, the Ontario Genomics Institute grants, and the National Cancer Institute of Canada with funds from the Canadian Cancer Society to J.F.G.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2005.01.007

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@article{7c1cca50535a4a0292a5290153275e9a,

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

abstract = "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.",

author = "Emre, {N. C Tolga} and Kristin Ingvarsdottir and Anastasia Wyce and Adam Wood and Krogan, {Nevan J.} and Henry, {Karl W.} and Keqin Li and Ronen Marmorstein and Greenblatt, {Jack F.} and Ali Shilatifard and Berger, {Shelley L.}",

note = "Funding Information: We thank M. Osley for HA-Ub expression plasmid, T. Edlind and K. Struhl for yeast strains, and Jean Dorsey for technical assistance. We acknowledge T. Krishnamoorthy, S. McMahon, and G. Moore for critically reading the manuscript. We thank the Berger lab and especially D. Gottschling for valuable discussions. Research was supported by research grants from the National Institutes of Health (NIH) and National Science Foundation to S.L.B; a National Research Service Award to K.W.H. and NIH training grant awards to K.W.H. and to A.W.; a doctoral fellowship from the University of Pennsylvania BGS to K.L.; the American Cancer Society, NIH, and a Mallinckrodt Foundation Award to A.S.; a doctoral fellowship from the Canadian Institutes of Health Research (CIHR) to N.J.K; the CIHR, the Ontario Genomics Institute grants, and the National Cancer Institute of Canada with funds from the Canadian Cancer Society to J.F.G. ",

year = "2005",

month = feb,

day = "18",

doi = "10.1016/j.molcel.2005.01.007",

language = "English (US)",

volume = "17",

pages = "585--594",

journal = "Molecular cell",

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T1 - Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing

AU - Emre, N. C Tolga

AU - Ingvarsdottir, Kristin

AU - Wyce, Anastasia

AU - Wood, Adam

AU - Krogan, Nevan J.

AU - Henry, Karl W.

AU - Li, Keqin

AU - Marmorstein, Ronen

AU - Greenblatt, Jack F.

AU - Shilatifard, Ali

AU - Berger, Shelley L.

N1 - Funding Information: We thank M. Osley for HA-Ub expression plasmid, T. Edlind and K. Struhl for yeast strains, and Jean Dorsey for technical assistance. We acknowledge T. Krishnamoorthy, S. McMahon, and G. Moore for critically reading the manuscript. We thank the Berger lab and especially D. Gottschling for valuable discussions. Research was supported by research grants from the National Institutes of Health (NIH) and National Science Foundation to S.L.B; a National Research Service Award to K.W.H. and NIH training grant awards to K.W.H. and to A.W.; a doctoral fellowship from the University of Pennsylvania BGS to K.L.; the American Cancer Society, NIH, and a Mallinckrodt Foundation Award to A.S.; a doctoral fellowship from the Canadian Institutes of Health Research (CIHR) to N.J.K; the CIHR, the Ontario Genomics Institute grants, and the National Cancer Institute of Canada with funds from the Canadian Cancer Society to J.F.G.

PY - 2005/2/18

Y1 - 2005/2/18

N2 - 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.

AB - 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.

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SN - 1097-2765

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JO - Molecular cell

JF - Molecular cell

IS - 4

ER -

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

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