Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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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Publications

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]

PMID: 24532716

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Project description:DEAD-box RNA helicases eIF4A and Ded1 are believed to promote translation initiation by resolving mRNA secondary structures that impede ribosome attachment at the mRNA 5’ end or subsequent scanning of the 5’UTR, but whether they perform distinct functions or act redundantly in vivo is poorly understood. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in yeast by ribosome footprint profiling. Despite similar reductions in bulk translation, inactivation of a cold-sensitive Ded1 mutant substantially reduced the TEs of >600 mRNAs, whereas inactivation of a temperature-sensitive eIF4A mutant yielded <40 similarly impaired mRNAs. The broader requirement for Ded1 did not reflect more pervasive secondary structures at low temperature, as inactivation of temperature-sensitive and cold-sensitive ded1 mutants gave highly correlated results. Interestingly, Ded1-dependent mRNAs exhibit greater than average 5’UTR length and propensity for secondary structure, implicating Ded1 in scanning though structured 5' UTRs. Reporter assays confirmed that cap- distal stem-loop insertions increase dependence on Ded1 but not eIF4A for efficient translation. While only a small fraction of mRNAs is strongly dependent on eIF4A, this dependence is significantly correlated with requirements for Ded1 and 5’UTR features characteristic of Ded1- dependent mRNAs. Our findings suggest that Ded1 is critically required to promote scanning through secondary structures within 5’UTRs; and while eIF4A cooperates with Ded1 in this function, it also promotes a step of initiation common to virtually all yeast mRNAs. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in yeast by ribosome footprint profiling.The study includes 32 samples, comprised of 16 mRNA-Seq samples and 16 ribosome footprint profiling samples, derived from biological replicates of 3 mutant strains, ded1-cs, ded1-ts and tif1-ts, and the corresponding wild-type strains. The tif1-ts mutant and its wild-type counterpart were analyzed at 30°C and 37°C.

Dataset Information

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

Publications

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

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