Unknown,Transcriptomics,Genomics,Proteomics

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Nucleosome loss leads to global transcriptional upregulation and genomic instability during yeast replicative aging


ABSTRACT: All eukaryotic cells divide a finite number of times, termed replicative aging, but the reason for this is not clear. Consistent with the decreased total histone protein levels in aged Saccharomyces cerevisiae, which is a cause of aging (1), we find that nucleosome occupancy decreases 50% across the whole genome during replicative aging by spike-in controlled MNase sequencing. Nucleosomes become fuzzier or move to sequences predicted to better accommodate histone octamers. All yeast genes are induced during aging. Genes that are repressed in young cells are most induced, accompanied by nucleosome loss from their promoters that have unique chromatin organization. Contrary to the loss of mitochondrial function during aging, mitochondrial DNA content increases and unprecedented levels of large-scale chromosomal alterations and increased retrotransposition are observed. Mnase-Seq experiments were carried out for young yeast, old yeast, and old yeast with histone over expression, 3 replicates were done for each category. RNA-Seq were carried out for the same categories of yeast cells but with 2 replicates for each. Genome-Seq were done for the young and old yeast with 2 replicates for each.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: kaifu chen 

PROVIDER: E-GEOD-47023 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Hu Zheng Z   Chen Kaifu K   Xia Zheng Z   Chavez Myrriah M   Pal Sangita S   Seol Ja-Hwan JH   Chen Chin-Chuan CC   Li Wei W   Tyler Jessica K JK  

Genes & development 20140201 4


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  ...[more]

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