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

Zheng Hu, Kaifu Chen, Zheng Xia, Myrriah Chavez, Sangita Pal, Ja Hwan Seol, Chin Chuan Chen, Wei Li, Jessica K. Tyler

Research output: Contribution to journalArticle

123 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)396-408
Number of pages13
JournalGenes and Development
Volume28
Issue number4
DOIs
StatePublished - Feb 15 2014

Keywords

  • DNA rearrangement
  • Gene expression
  • Histone occupancy
  • Replicative aging

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging'. Together they form a unique fingerprint.

  • Cite this

    Hu, Z., Chen, K., Xia, Z., Chavez, M., Pal, S., Seol, J. H., Chen, C. C., Li, W., & Tyler, J. K. (2014). Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. Genes and Development, 28(4), 396-408. https://doi.org/10.1101/gad.233221.113