Assay in which a heritable switch from red (middle) to green (top) fluorescence indicates a loss of silencing, meaning the frequency of green sectors in each colony (bottom) represents the frequency at which each strain loses silencing. Image credit: Saxton and Rine (CC BY 4.0)
A crucial process in life is the ability of cells to pass on useful information to their descendants. Some of this information is encoded within molecules of DNA, including genes that contain specific coded instructions. Another layer of information helps to specify whether individual genes are switched on or off, which means cells with the same genes can perform different tasks. However, it remains unclear exactly how cells pass on this additional layer of “epigenetic” information.
Inside human, yeast and other eukaryotic cells, DNA is wrapped around scaffold proteins known as histones. Cells modify histones by adding chemical tags to them, and histones within the same gene often have specific patterns of chemical tags. One popular hypothesis is that these marked histones constitute epigenetic information that may be passed on when DNA replicates before a cell divides to make two daughter cells. This model predicts that the marked histones need to be divided equally between the two sets of DNA to allow the epigenetic information to be faithfully passed on to both daughter cells.
To test this prediction, Saxton and Rine studied a gene called HMR that is involved in mating in yeast. This gene is constantly silenced (in other words, not actively providing instructions to the cell) and contains histones with very specific patterns of chemical tags. For the experiments, Saxton and Rine made a series of mutations in the yeast that increased how often these marked histones were divided unequally when the yeast cells replicated their DNA. Unexpectedly, these mutations had little impact on the ability of the cells to pass on the silenced state of HMR to their offspring. These findings argue against the classic model that marked histones carry epigenetic information.
