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SIRT6 is required for maintenance of telomere position effect in human cells

In Saccharomyces cerevisiae, the repressive chromatin environment at telomeres gives rise to telomere position effect (TPE), the epigenetic silencing of telomere-proximal genes. Chromatin-modifying factors that control TPE in yeast have been extensively studied, and among these, the lifespan regulat...

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Autores principales: Tennen, Ruth I., Bua, Dennis J., Wright, Woodring E., Chua, Katrin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528101/
https://www.ncbi.nlm.nih.gov/pubmed/21847107
http://dx.doi.org/10.1038/ncomms1443
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author Tennen, Ruth I.
Bua, Dennis J.
Wright, Woodring E.
Chua, Katrin F.
author_facet Tennen, Ruth I.
Bua, Dennis J.
Wright, Woodring E.
Chua, Katrin F.
author_sort Tennen, Ruth I.
collection PubMed
description In Saccharomyces cerevisiae, the repressive chromatin environment at telomeres gives rise to telomere position effect (TPE), the epigenetic silencing of telomere-proximal genes. Chromatin-modifying factors that control TPE in yeast have been extensively studied, and among these, the lifespan regulator and silencing protein Sir2 plays a pivotal role. In contrast, the factors that generate and maintain silent telomeric chromatin in human cells remain largely unknown. Here we show that the Sir2 family member SIRT6 is required for maintenance of TPE in human cells. RNAi-mediated depletion of SIRT6 abrogates silencing of both an integrated telomeric transgene and an endogenous telomere-proximal gene. Moreover, enhanced telomeric silencing in response to telomere elongation is associated with increased repressive chromatin marks, and this heterochromatic milieu is lost in SIRT6-deficient cells. Together, these findings establish a new role for SIRT6 in regulating an aging-associated epigenetic silencing process and provide new mechanistic insight into chromatin silencing at telomeres.
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spelling pubmed-35281012012-12-21 SIRT6 is required for maintenance of telomere position effect in human cells Tennen, Ruth I. Bua, Dennis J. Wright, Woodring E. Chua, Katrin F. Nat Commun Article In Saccharomyces cerevisiae, the repressive chromatin environment at telomeres gives rise to telomere position effect (TPE), the epigenetic silencing of telomere-proximal genes. Chromatin-modifying factors that control TPE in yeast have been extensively studied, and among these, the lifespan regulator and silencing protein Sir2 plays a pivotal role. In contrast, the factors that generate and maintain silent telomeric chromatin in human cells remain largely unknown. Here we show that the Sir2 family member SIRT6 is required for maintenance of TPE in human cells. RNAi-mediated depletion of SIRT6 abrogates silencing of both an integrated telomeric transgene and an endogenous telomere-proximal gene. Moreover, enhanced telomeric silencing in response to telomere elongation is associated with increased repressive chromatin marks, and this heterochromatic milieu is lost in SIRT6-deficient cells. Together, these findings establish a new role for SIRT6 in regulating an aging-associated epigenetic silencing process and provide new mechanistic insight into chromatin silencing at telomeres. 2011-08-16 /pmc/articles/PMC3528101/ /pubmed/21847107 http://dx.doi.org/10.1038/ncomms1443 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Tennen, Ruth I.
Bua, Dennis J.
Wright, Woodring E.
Chua, Katrin F.
SIRT6 is required for maintenance of telomere position effect in human cells
title SIRT6 is required for maintenance of telomere position effect in human cells
title_full SIRT6 is required for maintenance of telomere position effect in human cells
title_fullStr SIRT6 is required for maintenance of telomere position effect in human cells
title_full_unstemmed SIRT6 is required for maintenance of telomere position effect in human cells
title_short SIRT6 is required for maintenance of telomere position effect in human cells
title_sort sirt6 is required for maintenance of telomere position effect in human cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528101/
https://www.ncbi.nlm.nih.gov/pubmed/21847107
http://dx.doi.org/10.1038/ncomms1443
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