Aging Nucleosomes

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Science  07 Mar 2014:
Vol. 343, Issue 6175, pp. 1058-1059
DOI: 10.1126/science.343.6175.1058-d

DNA association with histone proteins to form nucleosomes provides barriers to transcription and replication and in this way provides careful regulation of these processes. As yeast age, histones are less prevalent and their overexpression is linked to increased life span. Given their regulatory nature, one might expect that a global loss of histones would result in increased expression of all genes; however, it has been reported that the expression of some genes goes up, whereas the expression of others goes down with aging. Hu et al. mapped nucleosome localization in aging yeast and revealed that nucleosomes became “fuzzier”—their positions became more variable along the DNA—and they showed a reduced periodicity, the tendency to recur at certain distances along the DNA. In contrast to studies showing increased repression of some genes during aging, a global loss of approximately 50% of nucleosomes correlated with the induction of expression of the entire genome. Furthermore, genes with the greatest induction contained sequences that more strongly assemble with nucleosomes. In addition to nucleosome loss and the induction of gene expression during aging, there was greater DNA damage at sites such as the ribosomal DNA locus and in mitochondrial DNA, as well as increased chromosomal trans locations. Whether similar changes in nucleosomes are associated with aging in higher eukaryotes is yet to be determined.

Genes Dev. 28, 396 (2014).

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