That DNA methylation studies change the way we perceive genetic regulation should be clear to anyone who has read last year’s Genome Biology special issue on epigenomics (if you haven’t yet – you definitely should!). Changes in DNA methylation have been associated with cancer, neurodevelopmental diseases and all sorts of metabolic disorders. The role of DNA methylation in cell differentiation and reprogramming has also been previously described.

In other words, DNA methylomics has become a convenient tool. Whenever some more or less inexplicable changes in the cell occur, you can say: look, DNA methylation is affected too! And it almost invariably will be. Which is why the rare studies demonstrating otherwise are so important: reminding us that in biology nothing ever follows just one obvious path. In this month’s issue of Genome Biology, we publish two such studies.

In the first of them, Rene Ketting and colleagues look at DNA methylation changes during the differentiation of intestinal cells in mice. They study these changes genome-wide and with an impressive single-base resolution, which is still quite a rarity in methylome studies, and monitor them across the transition from embryonic stem cells to terminally differentiated villus cells. And they find that, quite surprisingly, differential methylation throughout this process is very limited. This study comes hot on the heels of similar work from Alex Meissner’s lab, and is one of the very first to report such an unusual methylation dynamics during stem cell differentiation.

In our epigenomics issue, Jordana Bell and Tim Spector discussed an experimental setup in which differential DNA methylation is studied in monozygotic twins. Disease-discordant twin studies have so far proven to be an incredibly popular approach to epigenome-wide association studies, with recent publications on twins discordant for obesity, autism, breast cancer, diabetes, psioraris, and so on. Many, if not most, of these studies show that some differential DNA methylation can usually be observed. Enter Joern Walter and colleagues – authors of another article published in the May issue.

Walter and colleagues looked at DNA methylation in monozygotic twins discordant for birth weight. Hard as they tried, however, they did not manage to find any differences in DNA methylation above what would be expected from technical noise. Of note is the method the authors use to correct for saliva sample heterogeneity; and there is a cautionary tale hidden here: although a number of studies have recently reported that saliva can be used as a surrogate for other tissue types, not many of them acknowledged the uneven cell type composition of this source.

As it happens, we also publish two more twin-based studies in this issue. The story behind all our twin articles (sprinkled with twin-Gemini references) is described in another Genome Biology blog.