Keeping track of changes

Gene activity levels depend heavily on so-called ‘epigenetic’ modifications, such as the targeted addition of methyl chemical groups to individual cytosine nucleotides or to the histone proteins around which genomic DNA is wrapped.

Scientists have proposed that these two processes are closely linked, with the methylation state of the ‘tail’ domain of histone H3 directly affecting cytosine methylation within individual genes, and a new study from a team led by Jin-Qiu Zhou and Guo-Liang Xu at the Shanghai Institutes for Biological Sciences offers strong support for this model¹.

The researchers introduced mouse genes encoding DNA methyltransferase enzymes into yeast, which lack this pathway but retain an innate capacity for histone methylation, and noted that the activity of these enzymes was apparently blocked by methylation of a key lysine residue in the H3 tail, H3K4. In fact, DNA methylation was consistently absent at the actively transcribed gene loci where H3K4 methylation was markedly enriched; disruption of the histone methylation pathway in turn led to DNA methylation at previously unmarked sites.

They found that DNA modification is dependent on the capacity of DNA methyltransferases to bind directly to the H3 tail, and hypothesize that H3K4 modification helps activate genes by masking this binding site and thereby preventing DNA methylation-mediated repression.