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Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging

All eukaryotic cells divide a finite number of times, although the mechanistic basis of this replicative aging remains unclear. Replicative aging is accompanied by a reduction in histone protein levels, and this is a cause of aging in budding yeast. Here we show that nucleosome occupancy decreased b...

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Autores principales: Hu, Zheng, Chen, Kaifu, Xia, Zheng, Chavez, Myrriah, Pal, Sangita, Seol, Ja-Hwan, Chen, Chin-Chuan, Li, Wei, Tyler, Jessica K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937517/
https://www.ncbi.nlm.nih.gov/pubmed/24532716
http://dx.doi.org/10.1101/gad.233221.113
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author Hu, Zheng
Chen, Kaifu
Xia, Zheng
Chavez, Myrriah
Pal, Sangita
Seol, Ja-Hwan
Chen, Chin-Chuan
Li, Wei
Tyler, Jessica K.
author_facet Hu, Zheng
Chen, Kaifu
Xia, Zheng
Chavez, Myrriah
Pal, Sangita
Seol, Ja-Hwan
Chen, Chin-Chuan
Li, Wei
Tyler, Jessica K.
author_sort Hu, Zheng
collection PubMed
description All eukaryotic cells divide a finite number of times, although the mechanistic basis of this replicative aging remains unclear. Replicative aging is accompanied by a reduction in histone protein levels, and this is a cause of aging in budding yeast. Here we show that nucleosome occupancy decreased by 50% across the whole genome during replicative aging using spike-in controlled micrococcal nuclease digestion followed by sequencing. Furthermore, nucleosomes became less well positioned or moved to sequences predicted to better accommodate histone octamers. The loss of histones during aging led to transcriptional induction of all yeast genes. Genes that are normally repressed by promoter nucleosomes were most induced, accompanied by preferential nucleosome loss from their promoters. We also found elevated levels of DNA strand breaks, mitochondrial DNA transfer to the nuclear genome, large-scale chromosomal alterations, translocations, and retrotransposition during aging.
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spelling pubmed-39375172014-08-15 Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging Hu, Zheng Chen, Kaifu Xia, Zheng Chavez, Myrriah Pal, Sangita Seol, Ja-Hwan Chen, Chin-Chuan Li, Wei Tyler, Jessica K. Genes Dev Research Paper All eukaryotic cells divide a finite number of times, although the mechanistic basis of this replicative aging remains unclear. Replicative aging is accompanied by a reduction in histone protein levels, and this is a cause of aging in budding yeast. Here we show that nucleosome occupancy decreased by 50% across the whole genome during replicative aging using spike-in controlled micrococcal nuclease digestion followed by sequencing. Furthermore, nucleosomes became less well positioned or moved to sequences predicted to better accommodate histone octamers. The loss of histones during aging led to transcriptional induction of all yeast genes. Genes that are normally repressed by promoter nucleosomes were most induced, accompanied by preferential nucleosome loss from their promoters. We also found elevated levels of DNA strand breaks, mitochondrial DNA transfer to the nuclear genome, large-scale chromosomal alterations, translocations, and retrotransposition during aging. Cold Spring Harbor Laboratory Press 2014-02-15 /pmc/articles/PMC3937517/ /pubmed/24532716 http://dx.doi.org/10.1101/gad.233221.113 Text en © 2014 Hu et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Paper
Hu, Zheng
Chen, Kaifu
Xia, Zheng
Chavez, Myrriah
Pal, Sangita
Seol, Ja-Hwan
Chen, Chin-Chuan
Li, Wei
Tyler, Jessica K.
Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title_full Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title_fullStr Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title_full_unstemmed Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title_short Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
title_sort nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937517/
https://www.ncbi.nlm.nih.gov/pubmed/24532716
http://dx.doi.org/10.1101/gad.233221.113
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