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

TitleNucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging.
Publication TypeJournal Article
Year of Publication2014
AuthorsHu Z, Chen K, Xia Z, Chavez M, Pal S, Seol J-H, Chen C-C, Li W, Tyler JK
JournalGenes Dev
Date Published2014 Feb 15
KeywordsAging, Chromosome Aberrations, DNA Breaks, DNA, Mitochondrial, Gene Expression Regulation, Fungal, Genome, Fungal, Genomic Instability, Histones, Nucleosomes, Promoter Regions, Genetic, Saccharomyces cerevisiae, TATA Box, Up-Regulation

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.

Alternate JournalGenes Dev
PubMed ID24532716
PubMed Central IDPMC3937517
Grant ListR01HG007538 / HG / NHGRI NIH HHS / United States
GM64475 / GM / NIGMS NIH HHS / United States
CA95641 / CA / NCI NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700