Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast

Zheng Hu, Kaifu Chen, Wei Li, Jessica K. Tyler

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

All eukaryotic genomes are assembled into a nucleopro-tein structure termed chromatin, which is comprised of regular arrays of nucleosomes. Each nucleosome consists of eight core histone protein molecules around which the DNA is wrapped 1.75 times. The ultimate consequence of packaging the genome into chromatin is that the DNA sequences are relatively inaccessible. This allows the cell to use a comprehensive toolbox of chromatin-altering machineries to reveal access to the DNA sequence at the right time and right place in order to allow genomic processes, such as DNA repair, transcription and replication, to occur in a tightly-regulated manner. In other words, chromatin provides the framework that allows the regulation of all genomic processes, because the machineries that mediate transcription, repair and DNA replication themselves are relatively non-sequence specific and if the genome were naked, they would presumably perform their tasks in a random and unregulated manner. We recently provided support for this prediction in Zheng et al., [Genes and Development (2014) 28:396-408] by investigating a physiologically relevant scenario in which we had found that cells lose half of the core histone proteins, that is, during the mitotic aging (also called replicative aging) of budding yeast. Using new spike-in normalization techniques, we found that the occupancy of nucleosomes at most DNA sequences is reduced by 50%, leading to transcriptional induction of every single gene. This loss of histones during aging was also accompanied by a signifi-cantly-increased frequency of genomic instability including DNA breaks, chromosomal translocations, retrotrans-position, and transfer of mitochondrial DNA into the nuclear genome (Figure 1).

Original languageEnglish (US)
Pages (from-to)133-136
Number of pages4
JournalMicrobial Cell
Volume1
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Aging
  • DNA damage
  • Histones
  • Transcription
  • Translocation
  • Yeast

ASJC Scopus subject areas

  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Fingerprint Dive into the research topics of 'Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast'. Together they form a unique fingerprint.

Cite this