Confirming a long-held expectation that epigenetic as well as genetic information may be passed across generations, scientists have shown that a covalent histone modification can be preserved through multiple cell divisions, both mitotic and meiotic. The histone modification was artificially induced, via inactivation of a histone demethylase, but it mimicked a naturally occurring modification. It had the effect of switching off nearby genes, that is, genes that wrapped around the histone-complex “spools” containing altered histone.
Both the histone modification and its gene-deactivating effect were shown to be inherited independently of DNA sequence, DNA methylation, or RNA interference. This result, a clear demonstration that histone marks are epigenetically inheritable, appeared April 2 in the journal Science, in an article entitled, “Restricted epigenetic inheritance of H3K9 methylation.”
The article sums up research that was led by Robin Allshire, Ph.D., of the University of Edinburgh's School of Biological Sciences. “We've shown without doubt that changes in the histone spools that make up chromosomes can be copied and passed through generations,” said Dr. Allshire. “Our finding settles the idea that inherited traits can be epigenetic, meaning that they are not solely down to changes in a gene's DNA.”
According to a press release issued by the University of Edinburgh, the work led by Dr. Allshire could “pave the way for research into how and when this method of inheritance occurs in nature, and if it is linked to particular traits or health conditions.” In addition, it could “inform research into whether changes to the histone proteins that are caused by environmental conditions—such as stress or diet—can influence the function of genes passed on to offspring.”
Dr. Allshire’s team experimented with a fission yeast that uses gene control mechanisms similar to those in human cells. Specifically, the yeast is capable of histone H3 lysine 9 (H3K9) methylation, which is essential for heterochromatin formation. It happens that the yeast has a single H3K9 methyltransferase, Clr4, that directs all H3K9 methylation and heterochromatin.
“Using releasable tethered Clr4 reveals that an active process rapidly erases H3K9 methylation from tethering sites in wild-type cells,” wrote the authors of the Science article. “However, inactivation of the putative histone demethylase Epe1 allows H3K9 methylation and silent chromatin maintenance at the tethering site through many mitotic divisions, and transgenerationally through meiosis, after release of tethered Clr4.”
From these findings, the authors concluded that H3K9 methylation is a heritable epigenetic mark. Moreover, the transmission of this mark is usually countered because the mark is actively removed. When the mark is removed, the unauthorized inheritance of heterochromatin is prevented.