Review

Despite being heavily studied, we still don't understand the exact consequences of DNA methylation on gene expression. There is a positive association between cytosine methylation (5mC) in gene bodies and their transcriptional status. On the other hand, regulatory regions such as promoters or enhancers tend to be negatively correlated with gene expression, with CG density playing an important role. Moreover, physiological processes such as imprinting, or pathologies such as cancer, indicate that CpG island (CGI) methylation is strongly associated with gene silencing. It remains to be answered whether 5mC is a cause or a consequence of such silencing.
The authors of this preprint approach this interesting question, particularly at the level of gene promoters. To this end, they took advantage of the off-target effects of a zinc finger (ZF)-DNMT3A fusion protein (shown in their Fig 1A, below) originally designed to target a GC-rich 18 bp sequence in the SOX2 promoter.