Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast
Authors:Zheng Hu1, Kaifu Chen2, Wei Li2 and Jessica K. Tyler2
1 Department of Biochemistry and Molecular Biology, UT MD Anderson Cancer Center, 6767 Bertner Ave, Houston, TX 77030, USA.
2 Dan L Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Keywords:
DNA damage, translocation, transcription, histones, yeast, aging.
Related Article(s)?
Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol J, Chen C-C, Li W, and Tyler JK (2014). Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. Genes and Development 28:396-408. , 10.1101/gad.233221.113
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Zheng Hu, Kaifu Chen, Wei Li, and Jessica K. Tyler (2014). Transcriptional and genomic mayhem due to aging-induced nucleosome loss in budding yeast. Microbial Cell 1(4): 133-136.
© 2014 Hu et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
All eukaryotic genomes are assembled into a nucleoprotein 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 significantly-increased frequency of genomic instability including DNA breaks, chromosomal translocations, retrotransposition, and transfer of mitochondrial DNA into the nuclear genome (Figure 1).
doi: 10.15698/mic2014.04.139
Volume 1, pp. 133 to 136, published 01/04/2014.