title: Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Kaifu
authors.initials: K
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.forename: Myrriah
authors.initials: M
authors.lastname: Chavez
authors.forename: Sangita
authors.initials: S
authors.lastname: Pal
authors.forename: Ja-Hwan
authors.initials: JH
authors.lastname: Seol
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Tyler
mesh_terms: D000375:Aging / Q000235:genetics*; D002869:Chromosome Aberrations; D053960:DNA Breaks; D004272:DNA, Mitochondrial / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D009707:Nucleosomes / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D016385:TATA Box / Q000235:genetics; D015854:Up-Regulation
chemical_list: D004272:DNA, Mitochondrial; D006657:Histones; D009707:Nucleosomes
keywords: DNA rearrangement; gene expression; histone occupancy; replicative aging